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From SNPedia

Phenylketonuria (PKU) was one of the first inherited metabolic diseases to be tested for in newborns. PKU is a rare enzyme deficiency; only about 250 babies are born with this condition in the United States each year.

It is important to test for PKU because if it is not detected at birth, the enzyme deficiency will cause an entirely preventable form of mental retardation. An infant who inherits two copies of a mutation in the phenylalanine hydroxylase (PAH) gene cannot metabolize the amino acid phenylalanine found in proteins. With a normal diet, the phenylalanine level rises too high, and the baby develops brain damage and mental retardation.

Children with PKU who are given a strict low-phenylalanine diet from infancy will not develop brain damage. Common foods that contain phenylalanine include milk and eggs. The artificial sweetener NutraSweet (aspartame) contains phenylalanine, so food and drinks that use this sweetener are also banned from the PKU diet.

A woman with PKU who is or wants to become pregnant must be especially careful to follow a low-phenylalanine diet in order to avoid problems for the developing fetus.

For the full list of PKU-associated mutations in the PAH gene as of August 2016, curated based on the criteria listed below, see the following Table:

PAH Phenylketonuria Pathogenic Mutations
rsid 23andMe term synonyms (c. or p.) OMIM On chip?
rs62514891 i6016171 c.1A>G (p.Met1Val) 612349.0009
rs62514891 c.1A>T (p.Met1Leu)
rs62508575 rs62508575 c.2T>G (p.Met1Arg) 23andMe v3, 23andMe v4
rs62514893 rs62514893 c.3G>A (p.Met1Ile) 612349.0048 23andMe v3, 23andMe v4, Ancestry v2
rs62642906 rs62642906 c.47_48delCT (p.Ser16*)
rs199475585 i6016082 c.58C>T (p.Gln20*)
rs62514895 rs62514895 c.60+5G>T 23andMe v3, 23andMe v4
rs62514895 c.60+5G>A 23andMe v3, 23andMe v4
rs62514895 c.60+5G>C 23andMe v3, 23andMe v4
rs199475674 c.111dupG (p.Ile38Aspfs*19)
rs199475565 c.115_117delTTC (p.Phe39del)
rs762462102 c.116_118delTCT (p.Phe39del)
rs62642926 i4000470, rs62642926 c.c.117C>G (p.Phe39Leu) 612349.0031 23andMe v3
rs62642938 rs62642938 c.119C>T (p.Ser40Leu)
rs74603784 i5000102 c.136G>A (p.Gly46Ser) 612349.0055 Ancestry v2
rs199475591 c.137delG (p.Gly46Valfs*15)
rs5030841 rs5030841 c.c.143T>C (p.Leu48Ser) 612349.0034 23andMe v2, 23andMe v3, 23andMe v4, Ancestry v2
rs281865165 c.155delT (p.Leu52Cysfs*9)
rs199475631 c.163_165delTTT (p.Phe55del)
rs281865438 c.164T>C (p.Phe55Ser) Ancestry v2
rs199475566 c.165delT (p.Phe55Leufs*6) 612349.0037 Ancestry v2
rs199475598 c.165T>G (p.Phe55Leu) Ancestry v2
rs62507288 rs62507288 c.168+5G>A
rs62514898 rs62514898 c.168+1G>A 23andMe v3, 23andMe v4, Ancestry v2
rs62516144 rs62516144 c.168+6T>G
rs62507288 c.168+5G>C
rs62507288 c.168+5G>T
rs786204457 c.168_168+1delGGinsAA
rs62507341 rs62507341 c.169-13T>G
rs140945592 c.169G>T (p.Glu57*)
rs672601294 c.190delC (p.His64Thrfs*9)
rs75193786 i4000472, rs75193786 c.194T>C (p.Ile65Thr) 612349.0063
rs281865454 c.196G>T (p.Glu66*) Ancestry v2
rs5030842 rs5030842 c.199T>C (p.Ser67Pro)
rs199475687 c.206_208delCTT (p.Ser70del)
rs62642094 rs62642094 c.208_210delTCT (p.Ser70del)
rs762949770 c.226G>T (p.Glu76*)
rs62507332 rs62507332 c.231T>G (p.Tyr77*)
rs62509017 rs62509017 c.241A>C (p.Thr81Pro)
rs63749677 c.241_256del16 (p.Thr81Valfs*6)
rs62517202 c.266_267insG (p.Ala90Cysfs*12)
rs62508727 rs62508727 c.284_286_delTCA 612349.0030 23andMe v3, 23andMe v4
rs76296470 i4000473, rs76296470 c.331C>T (p.Arg111*) 612349.0005 Ancestry v2
rs199475648 c.344_347delAAGA (p.Lys115Thrfs*79)
rs281865428 c.350delC (p.Thr117Lysfs*78) Ancestry v2
rs199475684 c.352+1G>A
rs199475586 i6016403 c.359G>A (p.Trp120*)
rs199475605 c.398_401delATCA (p.Asn133Argfs*61)
rs199475680 i6016365 c.400C>T (p.Gln134*) Ancestry v2
rs199475599 i6016178 c.436C>T (p.His146Tyr)
rs199475624 i6016189 c.439C>T (p.Pro147Ser)
rs62507321 rs62507321 c.441+5G>T 23andMe v3, 23andMe v4, Ancestry v2
rs62508586 rs62508586 c.441+4A>G
rs62508642 rs62508642 c.441+3G>C
rs62517166 rs62517166 c.441+1G>A
rs199475698 c.441+6T>A
rs199475698 c.441+6T>C
rs62514907 c.442-1G>A 612349.0018 Ancestry v2
rs281865448 c.442-2A>C Ancestry v2
rs199475587 c.460T>C (p.Tyr154His)
rs199475612 c.471A>C (p.Arg157Ser)
rs75166491 i5053880, i6016098 c.472C>T (p.Arg158Trp)
rs5030843 i3003397, rs5030843 c.473G>A (p.Arg158Gln) 612349.0010 23andMe v2, 23andMe v3
rs199475626 c.493G>A (p.Ala165Thr)
rs199475645 i6016339 c.498C>A (p.Tyr166*)
rs199475645 c.498C>G (p.Tyr166*)
rs199475661 c.503delA (p.Tyr168Serfs*27)
rs281865455 c.504C>A (p.Tyr168*) Ancestry v2
rs62517175 rs62517175 c.509+5delG
rs62514911 c.509+1delG
rs63102461 c.509+1G>A
rs62507281 rs62507281 c.510-6T>A
rs62507281 c.510-6T>G
rs199475588 c.514C>T (p.Gln172*)
rs138809906 i6016126 c.521T>C (p.Ile174Thr)
rs199475575 i5000108 c.526C>T (p.Arg176*) Ancestry v2
rs199475671 i6016119 c.535T>C (p.Tyr179His)
rs199475671 c.535T>A (p.Tyr179Asn)
rs62507328 rs62507328 c.556delA (p.Thr186Hisfs*9)
rs62517207 c.558_559delAT (p.Trp187Glyfs*12)
rs62507336 rs62507336 c.561G>C (p.Trp187Cys) 23andMe v3, 23andMe v4
rs62507336 c.561G>A (p.Trp187*) 23andMe v3, 23andMe v4
rs62507260 rs62507260 c.563delG (p.Gly188Alafs*7)
rs62514919 rs62514919 c.569T>G (p.Val190Gly)
rs62508587 c.580_581delCT (p.Leu194Glufs*5) 23andMe v3
rs62895363 c.586_608del23 (p.Ser196Leufs*2)
rs63083561 c.590_612del23 (p.Leu197*)
rs281865442 i6016443 c.591G>C (p.Leu197Phe) Ancestry v2
rs199475697 c.592_613del22 (p.Tyr198Sserfs*136)
rs63749676 c.593_614del22 (p.Tyr198Cysfs*136)
rs1801147 rs1801147 c.609C>G (p.Cys203Trp)
rs62514927 rs62514927 c.611A>G (p.Ex6-96A>G) 612349.0013 23andMe v3, 23andMe v4, Ancestry v2
rs62514928 rs62514928 c.612T>G (p.Tyr204*)
rs63083560 rs63083560 c.613G>A (p.Glu205Lys)
rs62517201 rs62517201 c.618C>G (p.Tyr206*)
rs62517201 c.618C>A (p.Tyr206*)
rs62508572 rs62508572 c.619A>G (p.Asn207Asp)
rs62514929 rs62514929 c.632delC (p.Pro211Hisfs*130)
rs62516109 i6016236, rs62516109 c.638T>C (p.Leu213Pro) 23andMe v3, 23andMe v4, Ancestry v2
rs62509013 i6016347, rs62509013 c.648C>G (p.Tyr216*) 23andMe v3, 23andMe v4, Ancestry v2
rs62514936 rs62514936 c.663_664delAG (p.Asp222*)
rs759154440 c.664_665delGA (p.Asp222*)
rs62507323 rs62507323 c.671T>C (p.Ile224Thr)
rs199475589 i5900816 c.673C>G (p.Pro225Ala)
rs199475589 c.673C>A (p.Pro225Thr)
rs62508696 rs62508696 c.676C>T (p.Gln226*)
rs281865444 i6016298 c.682G>T (p.Glu228*) Ancestry v2
rs62508577 i6016377, rs62508577 c.692C>T (p.Ser231Phe)
rs62507348 rs62507348 c.694C>T (p.Gln232*) 23andMe v3, 23andMe v4, Ancestry v2
rs199475656 i6016153 c.704A>C (p.Gln235Pro)
rs62508592 rs62508592 c.706+17G>T
rs62507269 rs62507269 c.707-1G>A
rs62514938 c.707-2A>G
rs62517178 rs62517178 c.715G>A (p.Gly239Ser)
rs62507283 rs62507283 c.716G>T (p.Gly239Val)
rs62507283 c.716G>C (p.Gly239Ala)
rs76687508 i5900822 c.721C>T (p.Arg241Cys) Ancestry v2
rs199475657 c.722delG (p.Arg241Profs*100)
rs5030846 i3003398, rs5030846 c.727C>T (p.Arg243*) 612349.0011 Ancestry v2
rs62508588 i4000481, rs62508588 c.c.728G>A (p.Arg243Gln) 612349.0014 23andMe v3
rs118203923 i5900824, i6016195 c.c.731C>T (p.Pro244Leu) 612349.0047 Ancestry v2
rs199475666 c.737delC (p.Ala246Valfs*95)
rs62508731 c.739G>A (p.Gly247Ser)
rs199475579 c.740G>T (p.Gly247Val)
rs74503222 i5900826 c.745C>T (p.Leu249Phe) Ancestry v2
rs62507338 i6016237 c.746T>C (p.Leu249Pro)
rs5030847 i3003399, rs5030847 c.754C>T (p.Arg252Trp) 612349.0007 23andMe v2, 23andMe v3
rs5030847 c.754C>G (p.Arg252Gly) 23andMe v2, 23andMe v3
rs62644503 i5053886, i6016212 c.755G>A (p.Arg252Gln) Ancestry v2
rs62642930 rs62642930 c.764T>C (p.Leu255Ser) 612349.0026 23andMe v3, 23andMe v4, Ancestry v2
rs62642908 rs62642908 c.770G>T (p.Gly257Val)
rs62642932 i4000474, rs62642932 c.775G>A (p.Ala259Thr) 23andMe v3, Ancestry v2
rs118203921 i3002813 c.776C>T (p.Ala259Val) 612349.0028 Ancestry v2
rs5030850 i3003400, rs5030850 c.781C>T (p.Arg261*) 612349.0036 23andMe v2, 23andMe v3
rs5030849 i5012641, rs5030849 c.782G>A (p.Arg261Gln) 612349.0006 23andMe v1, 23andMe v2, 23andMe v3, 23andMe v4
rs62642944 c.789C>G (p.Phe263Leu)
rs62507335 i6016389, rs62507335 c.794G>A (p.Cys265Tyr)
rs199475676 i6016083 c.799C>T (p.Gln267*)
rs199475676 c.799C>G (p.Gln267Glu)
rs778154939 c.800A>G (p.Gln267Arg)
rs62508687 c.806delT (p.Ile269Thrfs*72) Ancestry v2
rs199475690 i6016157 c.808A>G (p.Arg270Gly)
rs62514950 rs62514950 c.809G>A (p.Arg270Lys) 23andMe v3, 23andMe v4, Ancestry v2
rs62514951 rs62514951 c.810A>T (p.Arg270Ser)
rs62507286 c.810_814delACATG (p.His271Ilefs*10)
rs62514952 i4000467 c.814G>T (p.Gly272*) 612349.0020 Ancestry v2
rs62514953 rs62514953 c.c.818C>T (p.Ser273Phe) 612349.0023 23andMe v3, 23andMe v4, Ancestry v2
rs78655458 i5053889, i6016323 c.829T>G (p.Tyr277Asp) 612349.0029 Ancestry v2
rs62507262 i6016086 c.833C>A (p.Thr278Asn)
rs62507262 c.833C>G (p.Thr278Ser)
rs62507262 c.833C>T (p.Thr278Ile)
rs281865429 c.837delC (p.Glu280Asnfs*61) Ancestry v2
rs62508698 i4000478 c.838G>A (p.Glu280Lys) 612349.0004 23andMe v3
rs199475668 c.838_842+3del8 (p.Glu280*)
rs62508734 rs62508734 c.839A>G (p.Glu280Gly)
rs199475653 c.839_840insT (p.Glu280Aspfs*3)
rs199475654 c.841C>T (p.Pro281Ser)
rs5030852 rs5030852 c.842+1G>A 612349.0025 23andMe v2, 23andMe v3, 23andMe v4
rs5030851 i3003401 c.842C>T (p.Pro281Leu) 612349.0012 Ancestry v2
rs62514955 c.842+2T>A 612349.0040 Ancestry v2
rs5030851 i6016194 c.842C>G (p.Pro281Arg) Ancestry v2
rs62507324 rs62507324 c.842+3G>C
rs62516146 rs62516146 c.842+5G>A 23andMe v3, 23andMe v4, Ancestry v2
rs5030852 c.842+1G>T 23andMe v2, 23andMe v3, 23andMe v4
rs62509019 rs62509019 c.843-2A>T
rs199475582 c.844G>A (p.Asp282Asn)
rs62508739 i6016382, rs62508739 c.856G>A (p.Glu286Lys)
rs62642910 i6016359 c.884C>G (p.Ser295*)
rs62507267 rs62507267 c.895_897delTTT (p.Phe299del)
rs62642933 i4000475, rs62642933 c.896T>G (p.Phe299Cys) 612349.0039 23andMe v3, Ancestry v2
rs62642920 rs62642920 c.904delT (p.Phe302fs*39)
rs199475592 c.911A>C (p.Gln304Pro)
rs62514956 rs62514956 c.912+1G>A 23andMe v3, 23andMe v4, Ancestry v2
rs281865450 c.912+3A>C Ancestry v2
rs281865449 c.912+2T>C Ancestry v2
rs62514956 c.912+1G>T 23andMe v3, 23andMe v4, Ancestry v2
rs62507264 rs62507264 c.913-5T>G
rs62517165 rs62517165 c.913-7A>G
rs281865452 c.913-8A>G Ancestry v2
rs281865456 c.916delA (p.Ile306Leufs*35) Ancestry v2
rs281865430 c.931_932delCT (p.Leu311Glyfs*4) Ancestry v2
rs62642936 rs62642936 c.932T>C (p.Leu311Pro) 612349.0003 23andMe v3, 23andMe v4, Ancestry v2
rs199475618 c.967_969delACA (p.Thr323del)
rs62517196 c.969+6T>A
rs62507273 rs62507273 c.970-5T>A
rs62507274 rs62507274 c.970-6T>G
rs62517199 rs62517199 c.970-2A>C
rs202183605 c.970-1G>A
rs202183605 c.970-1G>T
rs745670264 c.970-7A>G
rs62517199 c.970-2A>G
rs62508573 rs62508573 c.975C>G (p.Tyr325*)
rs62514959 rs62514959 c.977G>A (p.Trp326*) 612349.0015 23andMe v3, 23andMe v4, Ancestry v2
rs62517179 rs62517179 c.991T>C (p.Phe331Leu)
rs62508589 c.995G>T (p.Gly332Val)
rs62516060 rs62516060 c.997C>T (p.Leu333Phe) 612349.0050 23andMe v3, 23andMe v4, Ancestry v2
rs140243918 c.1002C>A (p.Cys334*)
rs62516061 rs62516061 c.1006C>T (p.Gln336*)
rs62517200 rs62517200 c.1021A>T (p.Lys341*)
rs62507282 rs62507282 c.1024G>C (p.Ala342Pro)
rs63581460 c.1024delG (p.Ala342Hisfs*58)
rs62508688 c.1036G>A (p.Gly346Arg)
rs62516063 rs62516063 c.1038delG (p.Leu347Serfs*53)
rs62508646 rs62508646 c.1045T>C (p.Ser349Pro) 612349.0041 23andMe v3, 23andMe v4
rs62507279 rs62507279 c.1046C>T (p.Ser349Leu)
rs62507279 c.1046C>A (p.Ser349*)
rs62517183 rs62517183 c.1048T>A (p.Ser350Thr)
rs62516094 rs62516094 c.1055delG (p.Gly352Valfs*48)
rs62507350 rs62507350 c.1056delT (p.Glu353Asnfs*47)
rs199475633 i6016084 c.1063C>T (p.Gln355*)
rs62516147 rs62516147 c.1065+1G>A 23andMe v3, 23andMe v4, Ancestry v2
rs62516147 c.1065+1G>T 23andMe v3, 23andMe v4, Ancestry v2
rs5030855 i5012636, rs5030855 c.1066-11G>A 612349.0033 23andMe v2, 23andMe v3, 23andMe v4, Ancestry v2
rs62507344 rs62507344 c.c.1066-3C>T 612349.0049
rs62507334 rs62507334 c.1066-14C>G
rs62508684 rs62508684 c.1066-1G>A
rs62516095 i4000479 c.1068C>G (p.Tyr356*) 612349.0019
rs62516095 c.1068C>A (p.Tyr356*)
rs766107583 i6016402 c.1071C>A (p.Cys357*)
rs5030854 i3003402 c.1076C>G (p.Ser359*) 612349.0052 Ancestry v2
rs62507329 rs62507329 c.1084C>A (p.Pro362Thr)
rs199475667 c.1087_1088delAA (p.Lys363Alafs*30)
rs5030654 c.1089delG (p.Lys363Asnfs*37) 23andMe v3, 23andMe v4
rs786200861 c.1092_1094delTCT (p.Leu365del) 612349.0021
rs62516097 c.c.1092_1106delTCTCCCCCTGGAGCT  (p.Leu365_Leu369del) 612349.0046
rs62508620 c.1099delC (p.Leu367Trpfs*33)
rs62516099 rs62516099 c.1117_1118delGC (p.Ala373Hisfs*20)
rs62642921 rs62642921 c.1127delA (p.Asn376Ilefs*24)
rs62642941 c.1129delT (p.Tyr377Thrfs*23) 612349.0061 23andMe v3, 23andMe v4
rs62516141 i6016354, rs62516141 c.1157A>G (p.Tyr386Cys) 23andMe v3, 23andMe v4, Ancestry v2
rs62517194 rs62517194 c.1159T>C (p.Tyr387His)
rs62517194 c.1159T>G (p.Tyr387Asp)
rs149595475 i6016344 c.1161C>A (p.Tyr387*)
rs62516101 i5053872, i6016216 c.1162G>A (p.Val388Met) 612349.0045
rs199475629 c.1163_1164delTG (p.Val388Glyfs*5)
rs62506949 rs62506949 c.1166delC (p.Ala389Glufs*11)
rs199475603 c.1196_1199delTAAG (p.Val399Glyfs*52)
rs281865436 c.1196T>C (p.Val399Ala) Ancestry v2
rs19945584 c.c.1197A>T (p.Val399=) 612349.0027
rs199475590 c.1198delA (p.Arg400Glyfs*52)
rs62508674 rs62508674 c.1199+5G>T
rs62508737 rs62508737 c.1199+2T>C
rs62509015 rs62509015 c.1199+1G>A 23andMe v3, 23andMe v4
rs62509018 rs62509018 c.1199+20G>C
rs62508674 c.1199+5G>A
rs62509015 c.1199+1G>C 23andMe v3, 23andMe v4
rs62507261 rs62507261 c.1200-8G>A
rs62507322 rs62507322 c.1200-1G>A 23andMe v3, 23andMe v4, Ancestry v2
rs63186960 c.1200-1delG
rs62644473 i5003360 c.c.1220C>T (p.Pro407Leu) 612349.0062 Ancestry v2
rs62644489 c.1220delC (p.Pro407Leufs*45)
rs5030858 i5012643, rs5030858 c.1222C>T (p.Arg408Trp) 612349.0002 23andMe v2, 23andMe v3, FTDNA2, FamilyTreeDNA, HumanOmni1Quad, 23andMe v4, Ancestry v2
rs5030859 i3003404, rs5030859 c.c.1223G>A  (p.Arg408Gln) 612349.0038 Ancestry v2
rs62644477 i6016361 c.1232C>G (p.Ser411*)
rs62644477 c.1232C>A (p.Ser411*)
rs79931499 rs28934899 c.1238G>C (p.Arg413Pro) 612349.0016 Ancestry v2
rs1801152 c.1242C>A (p.Tyr414*)
rs199475670 c.1271T>A (p.Leu424*)
rs5030861 i6050573, rs5030861 c.1315+1G>A 612349.0001 23andMe v2, 23andMe v3, 23andMe v4, Ancestry v2
rs1799970 rs1799970 c.1315+2T>C 23andMe v3, 23andMe v4, Ancestry v2
rs62508649 rs62508649 c.1315+4A>G
rs62508650 rs62508650 c.1315+6T>A
rs62509020 rs62509020 c.1316-5T>C
rs76542238 i6016274 c.1340C>A (p.Ala447Asp)

Mutations were considered pathogenic for phenylketonuria based on being listed as pathogenic in ClinVar and/or having an Assigned Value (AV) or Allelic Phenotype Value (APV) of less than 2 in the BioPKU PAHvdb database. Most mutations listed lead (when recessively inherited) to the classic PKU phenotype, however a few leading to somewhat milder phenotypes are included, for example when multiple ClinVar submitters consider the mutation pathogenic.