ATP6V1A (P38606) variants and mutations
ATP6V1A (also known as P38606) is a human protein-coding gene encoding a v-type proton ATPase catalytic subunit A protein. It provides ATP-hydrolyzing activity to the vacuolar proton pump, driving acidification of endosomes, lysosomes, and secretory vesicles. De novo pathogenic variants can cause developmental encephalopathy with epilepsy and intellectual disability. This analysis covers 725 ATP6V1A variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes genetic developmental and epileptic encephalopathy, developmental and epileptic encephalopathy 93, and neurodegenerative disease. Example ATP6V1A variants include D2E, D2G, and F3I.
Variant analysis overview
- Gene: ATP6V1A
- Protein: P38606
- UniProt accession: P38606
- Organism: Homo sapiens
- Variants analyzed: 725
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 542 unspecified-consequence records; 6 frameshift variants; 73 synonymous variants; 93 missense variants; 5 splice-region variants; 6 stop-gained variants
- Prediction scores: 505 variants have prediction scores (70% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: genetic developmental and epileptic encephalopathy, developmental and epileptic encephalopathy 93, neurodegenerative disease, Alzheimer disease, Parkinson disease, lysosomal storage disease, multiple sclerosis, autosomal recessive cutis laxa type 2, hereditary disease, cutis laxa, autosomal recessive cutis laxa type 2, classic type, undetermined early-onset epileptic encephalopathy.
Protein structure and variant hotspots
- Protein features: 1 binding sites; 3 post-translational modification sites.
- PTM context: 5 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable ATP6V1A variants
Examples include D2E, D2G, F3I, F3F, S4P, S4Y, S4S, K5E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- D2E (p.Asp2Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- D2G (p.Asp2Gly), Ensembl rs781561674, REVEL 0.49, CADD 26.00
- F3I (p.Phe3Ile), gnomAD rs1228715612, REVEL 0.32, CADD 23.70
- F3F (p.Phe3Phe), gnomAD 3-113778762-T-C, CADD 13.70
- S4P (p.Ser4Pro), gnomAD 3-113778758-AT-A, CADD 29.60
- S4Y (p.Ser4Tyr), gnomAD 3-113778764-C-A, REVEL 0.48, CADD 23.60
- S4S (p.Ser4Ser), gnomAD 3-113778765-C-T, CADD 10.40
- K5E (p.Lys5Glu), gnomAD 3-113778766-A-G, REVEL 0.34, CADD 23.20
- L6Q (p.Leu6Gln), gnomAD rs1269786889, REVEL 0.66, CADD 24.70
- L6I (p.Leu6Ile), gnomAD 3-113778769-C-A, REVEL 0.36, CADD 22.10
- L6P (p.Leu6Pro), gnomAD 3-113778770-T-C, REVEL 0.60, CADD 24.50
- P7A (p.Pro7Ala), gnomAD 3-113778772-C-G, REVEL 0.32, CADD 22.80
- P7S (p.Pro7Ser), gnomAD 3-113778772-C-T, REVEL 0.38, CADD 23.00
- P7T (p.Pro7Thr), gnomAD 3-113778772-C-A, REVEL 0.31, CADD 21.40
- P7H (p.Pro7His), gnomAD 3-113778773-C-A, REVEL 0.52, CADD 23.80
- P7P (p.Pro7Pro), gnomAD 3-113778774-C-T, CADD 11.10
- K8E (p.Lys8Glu), Ensembl rs1489067932
- K8R (p.Lys8Arg), TOPMed rs1376617803
- K8K (p.Lys8Lys), gnomAD 3-113778777-A-G, CADD 11.90
- I9T (p.Ile9Thr), Ensembl rs2108025434
- L10F (p.Leu10Phe), ExAC rs757699250, gnomAD rs757699250, REVEL 0.24, CADD 15.70
- L10I (p.Leu10Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L10R (p.Leu10Arg), rs781640990, ClinGen CA2547726, ClinVar RCV001532485, ExAC rs781640990, REVEL 0.24, CADD 9.68, Uncertain significance, not provided
- L10V (p.Leu10Val), gnomAD 3-113778781-C-G, REVEL 0.18, CADD 14.20
- L10P (p.Leu10Pro), gnomAD 3-113778782-T-C, REVEL 0.24, CADD 14.90
- L10L (p.Leu10Leu), gnomAD 3-113778783-C-A, CADD 2.47
- D11N (p.Asp11Asn), rs746407800, ClinGen CA2547728, NCI-TCGA Cosmic COSV5636, ClinVar RCV003052708, REVEL 0.30, CADD 22.80, Uncertain significance, not provided
- D11Y (p.Asp11Tyr), rs746407800, ClinGen CA2547727, ClinVar RCV003126309, ClinVar RCV006332221, REVEL 0.73, CADD 26.00, Uncertain significance, Inborn genetic diseases; Developmental and epileptic encephalopathy 93
- D11H (p.Asp11His), gnomAD 3-113778784-G-C, REVEL 0.50, CADD 23.30
- D11G (p.Asp11Gly), gnomAD 3-113778785-A-G, REVEL 0.48, CADD 24.30
- D11D (p.Asp11Asp), rs1452799014, gnomAD 3-113778786-T-C, CADD 9.42
- E12K (p.Glu12Lys), NCI-TCGA Cosmic COSV9985, REVEL 0.42, CADD 24.70, Variant assessed as somatic; moderate impact.
- E12D (p.Glu12Asp), gnomAD 3-113778789-A-T, REVEL 0.34, CADD 21.90
- D13Y (p.Asp13Tyr), gnomAD 3-113778790-G-T, REVEL 0.50, CADD 25.20
- D13G (p.Asp13Gly), gnomAD 3-113778791-A-G, REVEL 0.33, CADD 25.50
- K14E (p.Lys14Glu), TOPMed rs1398880626, gnomAD rs1398880626, REVEL 0.19, CADD 22.10
- E15D (p.Glu15Asp), TOPMed rs1197911761, gnomAD rs1197911761, REVEL 0.54, CADD 17.50
- E15Q (p.Glu15Gln), gnomAD 3-113778796-G-C, REVEL 0.75, CADD 27.50
- E15G (p.Glu15Gly), gnomAD 3-113778797-A-G, REVEL 0.84, CADD 27.20
- E15E (p.Glu15Glu), gnomAD 3-113778798-A-G, CADD 9.88
- S16I (p.Ser16Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S16R (p.Ser16Arg), TOPMed rs1475123226, Likely benign
- T17K (p.Thr17Lys), gnomAD 3-113778803-C-A, REVEL 0.15, CADD 17.60
- T17T (p.Thr17Thr), rs1708946714, gnomAD 3-113778804-A-C, CADD 8.97
- F18S (p.Phe18Ser), gnomAD 3-113778806-T-C, REVEL 0.60, CADD 23.50
- G19A (p.Gly19Ala), rs972975431, ClinGen CA354003412, ClinVar RCV003332565, AlphaMissense 0.99, MetaLR 0.89, Uncertain significance, not provided
- G19V (p.Gly19Val), Ensembl rs972975431, Uncertain significance, not provided
- G19C (p.Gly19Cys), gnomAD 3-113778808-G-T, REVEL 0.94, CADD 32.00
- G19S (p.Gly19Ser), gnomAD 3-113778808-G-A, REVEL 0.95, CADD 32.00
- Y20Y (p.Tyr20Tyr), rs775107680, gnomAD 3-113778813-T-C, CADD 11.00
- V21L (p.Val21Leu), ExAC rs748725125, gnomAD rs748725125, REVEL 0.79, CADD 24.00, Uncertain significance, Inborn genetic diseases; not provided
- V21E (p.Val21Glu), gnomAD 3-113778815-T-A, REVEL 0.93, CADD 28.10
- V21V (p.Val21Val), gnomAD 3-113778816-G-A, CADD 6.21
- H22R (p.His22Arg), rs768359551, ClinGen CA2547731, ClinVar RCV002932838, ClinVar RCV003269319, REVEL 0.34, CADD 22.60, Uncertain significance, Developmental and epileptic encephalopathy 93; Inborn genetic diseases; not prov
- H22Y (p.His22Tyr), gnomAD rs1233286633, REVEL 0.35, CADD 18.10
- G23E (p.Gly23Glu), Ensembl rs2108025475
- G23W (p.Gly23Trp), NCI-TCGA TCGA novel, REVEL 0.86, CADD 32.00, Variant assessed as somatic; moderate impact.
- G23G (p.Gly23Gly), gnomAD 3-113778822-G-T, CADD 7.59
- V24F (p.Val24Phe), gnomAD 3-113778823-G-T, REVEL 0.90, CADD 27.60
- V24I (p.Val24Ile), gnomAD 3-113778823-G-A, REVEL 0.51, CADD 24.10
- V24A (p.Val24Ala), gnomAD 3-113778824-T-C, REVEL 0.92, CADD 27.90
- S25A (p.Ser25Ala), gnomAD rs1708947071, REVEL 0.68, CADD 24.70
- S25P (p.Ser25Pro), gnomAD 3-113778826-T-C, REVEL 0.90, CADD 29.20
- S25W (p.Ser25Trp), gnomAD 3-113778826-TCA-T, CADD 28.50
- S25L (p.Ser25Leu), gnomAD 3-113778827-C-T, REVEL 0.88, CADD 29.90
- S25S (p.Ser25Ser), gnomAD 3-113778828-A-G, CADD 11.30
- G26G (p.Gly26Gly), gnomAD 3-113778831-A-G, CADD 13.70
- P27R (p.Pro27Arg), rs1553709380, ClinGen CA354003509, ClinVar RCV000656506, ClinVar RCV001266663, AlphaMissense 0.99, MetaLR 0.92, Pathogenic/Likely pathogenic, Inborn genetic diseases; not provided
- P27S (p.Pro27Ser), gnomAD 3-113778832-C-T, REVEL 0.81, CADD 25.70
- P27T (p.Pro27Thr), gnomAD 3-113778832-C-A, REVEL 0.93, CADD 25.40
- P27L (p.Pro27Leu), gnomAD 3-113778833-C-T, REVEL 0.90, CADD 33.00
- P27H (p.Pro27His), gnomAD 3-113778833-C-A, REVEL 0.88, CADD 32.00
- P27P (p.Pro27Pro), gnomAD 3-113778834-T-C, CADD 16.90
- V28L (p.Val28Leu), gnomAD 3-113778835-G-T, REVEL 0.76, CADD 33.00
- V28M (p.Val28Met), gnomAD 3-113778835-G-A, REVEL 0.87, CADD 35.00
- V28V (p.Val28Val), gnomAD 3-113781051-G-A, CADD 20.90
- V29L (p.Val29Leu), TOPMed rs1708971374
- T30A (p.Thr30Ala), rs760371089, ClinGen CA2547757, ClinVar RCV001311599, ExAC rs760371089, REVEL 0.55, CADD 24.00, Uncertain significance, not provided
- T30I (p.Thr30Ile), TOPMed rs1404147770, gnomAD rs1404147770, REVEL 0.34, CADD 22.30, Uncertain significance, not provided
- T30T (p.Thr30Thr), gnomAD 3-113781057-A-G, CADD 7.29
- A31S (p.Ala31Ser), NCI-TCGA Cosmic COSV9984, Variant assessed as somatic; moderate impact.
- A31T (p.Ala31Thr), gnomAD 3-113781058-G-A, REVEL 0.88, CADD 29.30
- A31A (p.Ala31Ala), rs1708971432, gnomAD 3-113781060-C-T, CADD 12.80
- D33Y (p.Asp33Tyr), Ensembl rs1559755073
- M34V (p.Met34Val), rs2549717399, ClinGen CA354004465, ClinVar RCV003731854, Uncertain significance, not provided
- A35E (p.Ala35Glu), ESP rs367827756, TOPMed rs367827756, gnomAD rs367827756, REVEL 0.42, CADD 21.00, Uncertain significance
- A35V (p.Ala35Val), rs367827756, ClinGen CA81618795, ClinVar RCV003821183, ClinVar RCV005934984, REVEL 0.38, CADD 22.90, Uncertain significance, not provided
- A35A (p.Ala35Ala), gnomAD 3-113781072-G-T, CADD 5.30
- G36S (p.Gly36Ser), gnomAD 3-113781073-G-A, REVEL 0.88, CADD 28.30
- G36G (p.Gly36Gly), rs202005300, gnomAD 3-113781075-T-C, CADD 9.68
- A37E (p.Ala37Glu), ExAC rs764290779, gnomAD rs764290779, REVEL 0.88, CADD 25.80
- A37G (p.Ala37Gly), ExAC rs764290779, gnomAD rs764290779, REVEL 0.74, CADD 23.90
- A37T (p.Ala37Thr), ExAC rs759487334, gnomAD rs759487334, REVEL 0.65, CADD 25.00
- A37A (p.Ala37Ala), rs762168039, gnomAD 3-113781078-A-G, CADD 10.80
- A38S (p.Ala38Ser), ExAC rs767614324
- A38D (p.Ala38Asp), gnomAD 3-113781080-C-A, REVEL 0.90, CADD 26.50
- M39I (p.Met39Ile), rs2549717420, ClinGen CA354004600, ClinVar RCV003291730, REVEL 0.82, CADD 24.80, Uncertain significance, Inborn genetic diseases
- M39L (p.Met39Leu), ExAC rs750858415, REVEL 0.78, CADD 25.40
- Y40F (p.Tyr40Phe), Ensembl rs1708971781, REVEL 0.56, CADD 22.90
- Y40* (p.Tyr40Ter), gnomAD 3-113781087-T-G, CADD 35.00
- E41* (p.Glu41Ter), gnomAD 3-113781088-G-T, CADD 40.00
- V43G (p.Val43Gly), ExAC rs756435196, gnomAD rs756435196, REVEL 0.77, CADD 29.30
- V43L (p.Val43Leu), NCI-TCGA Cosmic COSV9984, Variant assessed as somatic; moderate impact.
- V43V (p.Val43Val), rs780402818, gnomAD 3-113781096-G-A, CADD 13.00
- R44T (p.Arg44Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R44S (p.Arg44Ser), gnomAD 3-113781095-TGA-T, CADD 31.00
- R44G (p.Arg44Gly), gnomAD 3-113781097-A-G, REVEL 0.54, CADD 26.20
- V45G (p.Val45Gly), ExAC rs754359607, gnomAD rs754359607
- V45V (p.Val45Val), rs1708971917, gnomAD 3-113781102-G-C, CADD 10.50
- G46V (p.Gly46Val), gnomAD 3-113781104-G-T, REVEL 0.61, CADD 27.40
- G46G (p.Gly46Gly), gnomAD 3-113781105-C-A, CADD 9.87
- H47H (p.His47His), gnomAD 3-113781108-C-T, CADD 10.70
- S48I (p.Ser48Ile), NCI-TCGA Cosmic COSV5636, Variant assessed as somatic; moderate impact.
- S48S (p.Ser48Ser), rs755432094, gnomAD 3-113781111-C-T, CADD 4.11
- E49K (p.Glu49Lys), rs778431937, ClinGen CA2547770, NCI-TCGA Cosmic COSV5636, ClinVar RCV002672146, REVEL 0.20, CADD 22.90, Uncertain significance, not provided
- E49V (p.Glu49Val), ExAC rs747631097, gnomAD rs747631097, REVEL 0.33, CADD 23.50
- E49* (p.Glu49Ter), gnomAD 3-113781112-G-T, CADD 37.00
- E49E (p.Glu49Glu), rs1190593959, gnomAD 3-113781114-A-G, CADD 11.40
- L50F (p.Leu50Phe), NCI-TCGA Cosmic COSV5636, Variant assessed as somatic; moderate impact.
- L50V (p.Leu50Val), ExAC rs771765985, gnomAD rs771765985, REVEL 0.77, CADD 22.00
- L50L (p.Leu50Leu), rs771765985, gnomAD 3-113781115-T-C, CADD 7.86
- G52R (p.Gly52Arg), gnomAD 3-113781121-G-A, REVEL 0.93, CADD 32.00
- G52G (p.Gly52Gly), gnomAD 3-113781123-A-C, CADD 13.80
- E53K (p.Glu53Lys), rs2549717458, ClinGen CA354005005, ClinVar RCV003041111, Uncertain significance, not provided
- E53Q (p.Glu53Gln), NCI-TCGA Cosmic COSV5636, Variant assessed as somatic; moderate impact.
- I54M (p.Ile54Met), ESP rs371639275, ExAC rs371639275, TOPMed rs371639275, gnomAD rs371639275, REVEL 0.80, CADD 23.90
- I54T (p.Ile54Thr), Ensembl rs1708972132
- I54I (p.Ile54Ile), gnomAD 3-113781129-T-A, CADD 11.90
- R56* (p.Arg56Ter), NCI-TCGA Cosmic COSV5636, CADD 38.00, Variant assessed as somatic; high impact.
- R56Q (p.Arg56Gln), Ensembl rs1708972204
- R56R (p.Arg56Arg), gnomAD 3-113781133-C-A, CADD 20.40
- R56L (p.Arg56Leu), gnomAD 3-113781134-G-T, REVEL 0.92, CADD 31.00
- L57L (p.Leu57Leu), rs1450732273, gnomAD 3-113781136-T-C, CADD 7.17
- E58D (p.Glu58Asp), TOPMed rs1315496967, gnomAD rs1315496967, REVEL 0.39, CADD 16.00
- E58A (p.Glu58Ala), gnomAD 3-113781140-A-C, REVEL 0.91, CADD 27.40
- G59D (p.Gly59Asp), gnomAD rs1379328654, REVEL 0.45, CADD 24.50
- G59V (p.Gly59Val), gnomAD 3-113781143-G-T, REVEL 0.71, CADD 27.20
- M61I (p.Met61Ile), rs1218012061, ClinGen CA354005280, ClinVar RCV002635085, ClinVar RCV004065904, REVEL 0.11, CADD 22.80, Uncertain significance, Inborn genetic diseases; not provided
- M61T (p.Met61Thr), rs2549717471, ClinGen CA354005273, ClinVar RCV003864023, Uncertain significance, not provided
- A62S (p.Ala62Ser), Ensembl rs2108027168
- A62T (p.Ala62Thr), gnomAD 3-113781151-G-A, REVEL 0.86, CADD 27.40
- A62A (p.Ala62Ala), rs770644270, gnomAD 3-113781153-T-G, CADD 8.92
- T63N (p.Thr63Asn), gnomAD rs1467990504
- I64V (p.Ile64Val), ESP rs140326941, TOPMed rs140326941, gnomAD rs140326941, REVEL 0.42, CADD 21.40
- Q65E (p.Gln65Glu), NCI-TCGA Cosmic COSV5636, Variant assessed as somatic; moderate impact.
- Q65Q (p.Gln65Gln), rs1175455456, gnomAD 3-113781162-G-A, CADD 7.43
- V66G (p.Val66Gly), Ensembl rs1577088619
- V66V (p.Val66Val), rs776436157, gnomAD 3-113781165-G-A, CADD 19.10
- Y67C (p.Tyr67Cys), TOPMed rs1394292766, gnomAD rs1394292766, REVEL 0.93, CADD 33.00
- Y67Y (p.Tyr67Tyr), rs113065914, gnomAD 3-113781168-T-C, CADD 9.45
- T70S (p.Thr70Ser), gnomAD 3-113781175-A-T, REVEL 0.85, CADD 23.80
- S71L (p.Ser71Leu), gnomAD 3-113781176-CT-C, CADD 13.80
- G72D (p.Gly72Asp), rs1060505037, ClinGen CA16616874, NCI-TCGA Cosmic COSV5636, ClinVar RCV000477689, AlphaMissense 0.79, MetaLR 0.93, Pathogenic, Autosomal recessive cutis laxa type 2D
- G72G (p.Gly72Gly), rs769912385, gnomAD 3-113784228-T-C, CADD 12.00
- V73G (p.Val73Gly), TOPMed rs1289283540
- V73L (p.Val73Leu), TOPMed rs981146211, gnomAD rs981146211, REVEL 0.36, AlphaMissense 0.34
- V73M (p.Val73Met), rs981146211, ClinGen CA354006962, ClinVar RCV002512231, AlphaMissense 0.34, MetaLR 0.23, Uncertain significance, not provided
- V73A (p.Val73Ala), gnomAD 3-113784230-T-C, REVEL 0.82, CADD 28.20
- S74A (p.Ser74Ala), rs2549719151, ClinGen CA354006995, ClinVar RCV003030332, Uncertain significance, not provided
- V75F (p.Val75Phe), rs775563385, ClinGen CA2547796, ClinVar RCV003846937, ClinVar RCV004968510, REVEL 0.56, CADD 28.40, Uncertain significance, not provided; Inborn genetic diseases
- G76A (p.Gly76Ala), gnomAD 3-113784239-G-C, REVEL 0.86, CADD 32.00
- P78P (p.Pro78Pro), rs1207953955, gnomAD 3-113784246-T-C, CADD 13.90
- V79V (p.Val79Val), gnomAD 3-113784249-A-G, AlphaMissense 0.14, MetaLR 0.38
- L80F (p.Leu80Phe), TOPMed rs1709013502, gnomAD rs1709013502, REVEL 0.23, AlphaMissense 0.12
- L80V (p.Leu80Val), gnomAD 3-113784250-C-G, REVEL 0.17, AlphaMissense 0.43
- R81C (p.Arg81Cys), rs1283020403, NCI-TCGA Cosmic COSV5636, gnomAD rs1283020403, REVEL 0.69, CADD 25.30, Uncertain significance, not provided
- R81H (p.Arg81His), rs1351534048, NCI-TCGA Cosmic COSV9985, TOPMed rs1351534048, gnomAD rs1351534048, REVEL 0.68, CADD 32.00, Uncertain significance, not provided
- T82S (p.Thr82Ser), ExAC rs749171534, gnomAD rs749171534, REVEL 0.61, CADD 21.30
- G83D (p.Gly83Asp), rs1709013687, ClinGen CA354007210, ClinVar RCV002227693, Ensembl rs1709013687, REVEL 0.77, CADD 29.90, Uncertain significance, Developmental and epileptic encephalopathy 93
- G83S (p.Gly83Ser), rs778615930, ClinGen CA2547798, ClinVar RCV001874644, ExAC rs778615930, REVEL 0.70, CADD 28.90, Uncertain significance, not provided
- G83C (p.Gly83Cys), gnomAD 3-113784259-G-T, REVEL 0.68, CADD 26.30
- G83G (p.Gly83Gly), gnomAD 3-113784261-T-G, CADD 11.30
- K84N (p.Lys84Asn), NCI-TCGA Cosmic COSV5636, Ensembl rs1577089719, Variant assessed as somatic; moderate impact.
- P85T (p.Pro85Thr), rs2108029577, ClinGen CA354007237, ClinVar RCV001886391, Ensembl rs2108029577, AlphaMissense 0.86, MetaLR 0.41, Uncertain significance, not provided
- P85P (p.Pro85Pro), gnomAD 3-113784267-C-T, CADD 9.33
- L86V (p.Leu86Val), gnomAD 3-113784268-C-G, REVEL 0.43, CADD 24.80
- L86L (p.Leu86Leu), gnomAD 3-113784270-C-G, CADD 8.40
- S87C (p.Ser87Cys), ExAC rs773297197, gnomAD rs773297197, REVEL 0.31, CADD 23.60, Uncertain significance, not provided
- S87F (p.Ser87Phe), NCI-TCGA Cosmic COSV5636, Variant assessed as somatic; moderate impact.
- V88A (p.Val88Ala), rs760842074, NCI-TCGA Cosmic COSV5636, ExAC rs760842074, gnomAD rs760842074, REVEL 0.54, CADD 27.90, Variant assessed as somatic; moderate impact.
Public ATP6V1A analysis runs
- ATP6V1A analysis run — ATP6V1A (725 variants) — completed 2026-08-20