ABCC8 (Q09428) variants and mutations
ABCC8 (also known as Q09428) is a human protein-coding gene encoding an ATP-binding cassette sub-family C member 8 protein. It senses cellular nucleotide levels as the regulatory component of pancreatic beta-cell ATP-sensitive potassium channels and thereby couples glucose metabolism to insulin secretion. Loss-of-function variants cause congenital hyperinsulinism, whereas activating variants can cause neonatal diabetes. This analysis covers 2,466 ABCC8 variants and mutations. Of these, 69% have computational variant effect predictions. Disease context includes type 2 diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1, and diabetes mellitus, permanent neonatal 3. Example ABCC8 variants include M1T, M1V, and P2S.
Variant analysis overview
- Gene: ABCC8
- Protein: Q09428
- UniProt accession: Q09428
- Organism: Homo sapiens
- Variants analyzed: 2466
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,267 unspecified-consequence records; 81 synonymous variants; 95 missense variants; 3 in-frame deletions; 5 splice-region variants; 5 frameshift variants; 5 stop-gained variants; 5 substitution
- Prediction scores: 1,692 variants have prediction scores (69% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: type 2 diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 1, diabetes mellitus, permanent neonatal 3, diabetes mellitus, transient neonatal, 2, diabetes mellitus, leucine-induced hypoglycemia, permanent neonatal diabetes mellitus, transient neonatal diabetes mellitus, autosomal dominant hyperinsulinism due to SUR1 deficiency, Hypoglycemia, diazoxide-resistant focal hyperinsulinism due to SUR1 deficiency, MODY.
Protein structure and variant hotspots
- Protein features: 17 transmembrane segments; 4 domains; 13 binding sites; 2 post-translational modification sites.
- Structural context: 1,809 variants have structural context.
- PTM context: 1 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, ClinGen, MaveDB, LitVar.
Notable ABCC8 variants
Examples include M1T, M1V, P2S, P2T, L3V, A4P, A4S, A4V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs2496931463, ClinGen CA379790501, ClinVar RCV003681280, Pathogenic, not provided
- M1V (p.Met1Val), rs2496931481, ClinGen CA379790517, ClinVar RCV003062345, ClinVar RCV005045198, Pathogenic/Likely pathogenic, Diabetes mellitus, permanent neonatal 3; Diabetes mellitus, transient neonatal
- P2S (p.Pro2Ser), rs756552692, ClinGen CA5904003, ClinVar RCV002254255, ClinVar RCV002254256, REVEL 0.19, CADD 17.30, Uncertain significance, Inborn genetic diseases; Maturity-onset diabetes of the young; Transitory neonat
- P2T (p.Pro2Thr), rs756552692, ClinGen CA379790485, ClinVar RCV001280387, ClinVar RCV002486074, REVEL 0.21, CADD 19.80, Uncertain significance, not provided; ABCC8-related disorder; Type 2 diabetes mellitus
- L3V (p.Leu3Val), TOPMed rs1206338992, gnomAD rs1206338992, REVEL 0.45, CADD 20.80, Uncertain significance, Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familia
- A4P (p.Ala4Pro), cosmic curated COSV10884
- A4S (p.Ala4Ser), cosmic curated COSV56854
- A4V (p.Ala4Val), rs2133738359, ClinGen CA379790450, ClinVar RCV001353383, ClinVar RCV004526116, REVEL 0.71, CADD 28.20, Conflicting interpretations, not specified; Hyperinsulinemic hypoglycemia, familial, 1
- C6R (p.Cys6Arg), gnomAD rs1848810190, REVEL 0.89, CADD 32.00
- G7C (p.Gly7Cys), rs781059815, ClinGen CA379790383, ClinVar RCV003665580, REVEL 0.90, CADD 32.00, Likely pathogenic, not provided
- G7D (p.Gly7Asp), rs1848809864, ClinGen CA379790378, ClinVar RCV002889171, ClinVar RCV004700847, REVEL 0.86, CADD 28.10, Conflicting interpretations, not specified; not provided
- G7R (p.Gly7Arg), rs781059815, ClinGen CA218464119, ClinVar RCV003058290, ClinVar RCV003317639, REVEL 0.95, CADD 31.00, Likely pathogenic, ABCC8-related disorder; Hyperinsulinemic hypoglycemia, familial, 1; not provided
- G7S (p.Gly7Ser), ExAC rs781059815, TOPMed rs781059815, gnomAD rs781059815, REVEL 0.87, CADD 30.00, Uncertain significance, not specified
- S8G (p.Ser8Gly), TOPMed rs1848809505, gnomAD rs1848809505, REVEL 0.20, CADD 22.60
- S8I (p.Ser8Ile), Ensembl rs1591935147, REVEL 0.21, CADD 23.10, Uncertain significance, Hereditary hyperinsulinism
- H11Y (p.His11Tyr), ExAC rs751082043, TOPMed rs751082043, gnomAD rs751082043, REVEL 0.23, CADD 22.80, Uncertain significance, not provided
- S12* (p.Ser12Ter), rs1283621955, ClinGen CA379790231, ClinVar RCV001212753, ClinVar RCV001779134, AlphaMissense 0.18, MetaLR 0.64, Pathogenic
- S12L (p.Ser12Leu), rs1283621955, ClinGen CA379790233, ClinVar RCV002254253, ClinVar RCV002254254, AlphaMissense 0.18, MetaLR 0.64, Uncertain significance, Transitory neonatal diabetes mellitus; Maturity-onset diabetes of the young
- S12W (p.Ser12Trp), TOPMed rs1283621955, gnomAD rs1283621955, Pathogenic
- A13T (p.Ala13Thr), gnomAD rs1343830800, REVEL 0.13, CADD 18.40
- A14S (p.Ala14Ser), gnomAD rs1298051389, REVEL 0.38, CADD 21.70
- Y15* (p.Tyr15Ter), rs758231286, ClinGen CA379790178, ClinVar RCV001910791, ClinVar RCV002490136, CADD 37.00, Pathogenic
- R16L (p.Arg16Leu), cosmic curated COSV56855, REVEL 0.29, CADD 24.80
- R16Q (p.Arg16Gln), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, NCI-TCGA Cosmic COSV5685, Variant assessed as somatic; moderate impact.
- R16W (p.Arg16Trp), rs1591935006, ClinGen CA379790172, NCI-TCGA Cosmic COSV5684, cosmic curated COSV56849, AlphaMissense 0.21, MetaLR 0.47, Uncertain significance, not specified
- V17A (p.Val17Ala), rs764950519, ClinGen CA5903995, ClinVar RCV001817905, ClinVar RCV003321876, REVEL 0.52, CADD 28.60, Conflicting interpretations, Hyperinsulinemic hypoglycemia, familial, 1; Type 2 diabetes mellitus; not provid
- D18G (p.Asp18Gly), TOPMed rs1848806669, gnomAD rs1848806669, REVEL 0.44, CADD 24.20
- D18N (p.Asp18Asn), ExAC rs761650987, gnomAD rs761650987, REVEL 0.23, CADD 22.50
- Q19* (p.Gln19Ter), rs1407486337, ClinGen CA379790127, ClinVar RCV003322281, gnomAD rs1407486337, CADD 36.00, Pathogenic
- Q19H (p.Gln19His), TOPMed rs1848806338, gnomAD rs1848806338, REVEL 0.22, CADD 17.20
- G20A (p.Gly20Ala), Ensembl rs969644157
- V21D (p.Val21Asp), rs200670692, ClinGen CA5903992, ClinVar RCV000588969, ClinVar RCV000666072, REVEL 0.86, CADD 32.00, Pathogenic/Likely pathogenic, not provided; Familial hyperinsulinism; ABCC8-related disorder
- V21F (p.Val21Phe), rs1176097396, ClinGen CA379790100, ClinVar RCV003875905, REVEL 0.79, CADD 28.70, Likely pathogenic, not provided
- V21I (p.Val21Ile), rs1176097396, ClinGen CA379790102, ClinVar RCV003322280, TOPMed rs1176097396, REVEL 0.62, CADD 26.70, Uncertain significance, Hyperinsulinemic hypoglycemia, familial, 1
- L22F (p.Leu22Phe), NCI-TCGA Cosmic COSV5685, cosmic curated COSV56857, Variant assessed as somatic; moderate impact.
- N23D (p.Asn23Asp), ExAC rs774248683, REVEL 0.32, AlphaMissense 0.15
- N23H (p.Asn23His), rs774248683, ClinGen CA379790082, ClinVar RCV003665579, AlphaMissense 0.15, MetaLR 0.75, Likely pathogenic, not provided
- N23K (p.Asn23Lys), TOPMed rs1022337682, REVEL 0.43, CADD 24.00
- N24K (p.Asn24Lys), rs771075821, ClinGen CA248475, ClinVar RCV000201893, ClinVar RCV003321541, REVEL 0.86, CADD 26.70, Uncertain significance, Congenital isolated hyperinsulinism
- G25S (p.Gly25Ser), gnomAD rs1428579443, REVEL 0.50, CADD 24.50, Uncertain significance, Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familia
- G25V (p.Gly25Val), rs763302648, ClinGen CA5903988, ClinVar RCV001108381, ClinVar RCV001108382, REVEL 0.43, CADD 22.70, Uncertain significance, Hyperinsulinemic hypoglycemia, familial, 1; Transitory neonatal diabetes mellitu
- C26R (p.Cys26Arg), TOPMed rs1462559571, gnomAD rs1462559571, Pathogenic
- C26S (p.Cys26Ser), rs1462559571, ClinGen CA379790058, ClinVar RCV001817862, ClinVar RCV001844417, REVEL 0.92, CADD 31.00, Conflicting interpretations, Hyperinsulinemic hypoglycemia, familial, 1; Diabetes mellitus, transient neonata
- C26W (p.Cys26Trp), gnomAD rs1263713686, REVEL 0.88, CADD 32.00
- F27L (p.Phe27Leu), TOPMed rs1202763483, gnomAD rs1202763483, REVEL 0.65, CADD 23.10, Uncertain significance, in HHF1
- F27S (p.Phe27Ser), rs2496930367, ClinGen CA379790046, ClinVar RCV003557578, UniProt VAR 031351, REVEL 0.96, CADD 32.00, Likely pathogenic, not provided
- F27V (p.Phe27Val), rs1202763483, ClinGen CA379790048, ClinVar RCV001889788, TOPMed rs1202763483, AlphaMissense 0.99, MetaLR 0.75, Uncertain significance, not provided
- V28M (p.Val28Met), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, Variant assessed as somatic; moderate impact.
- D29G (p.Asp29Gly), rs1591934736, ClinGen CA379790032, ClinVar RCV003236419, Ensembl rs1591934736, REVEL 0.90, CADD 33.00, Uncertain significance, not specified
- D29N (p.Asp29Asn), cosmic curated COSV10440
- D29V (p.Asp29Val), Ensembl rs1591934736, Uncertain significance
- A30T (p.Ala30Thr), rs1474215749, ClinGen CA379790027, ClinVar RCV004543958, ClinVar RCV006479054, REVEL 0.63, CADD 28.90, Uncertain significance, not provided
- A30V (p.Ala30Val), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, REVEL 0.66, CADD 32.00, Variant assessed as somatic; moderate impact.
- L31F (p.Leu31Phe), ExAC rs780968014, gnomAD rs780968014, REVEL 0.80, CADD 26.10
- N32K (p.Asn32Lys), rs2496930134, ClinGen CA379790011, ClinVar RCV003463382, ClinVar RCV003553964, REVEL 0.65, CADD 23.40, Pathogenic, Familial hyperinsulinism; Type 2 diabetes mellitus; not provided
- N32S (p.Asn32Ser), rs1848801744, ClinGen CA379790013, NCI-TCGA Cosmic COSV5684, cosmic curated COSV56847, REVEL 0.60, CADD 23.40, Likely pathogenic, not provided
- V33L (p.Val33Leu), rs768372267, ExAC rs768372267, gnomAD rs768372267, ClinGen CA379790008, AlphaMissense 0.29, MetaLR 0.67, Uncertain significance, Diabetes mellitus, transient neonatal, 2; Leucine-induced hypoglycemia; Type 2 d
- V33M (p.Val33Met), rs768372267, ClinGen CA5903983, ClinVar RCV002254367, ClinVar RCV002254368, REVEL 0.49, AlphaMissense 0.29, Uncertain significance, Transitory neonatal diabetes mellitus; Maturity-onset diabetes of the young
- V34G (p.Val34Gly), Ensembl rs1591934613
- V34M (p.Val34Met), cosmic curated COSV56854
- P35L (p.Pro35Leu), TOPMed rs990625730, REVEL 0.85, CADD 32.00
- P35S (p.Pro35Ser), rs1183465672, ClinGen CA379789992, ClinVar RCV000666845, ClinVar RCV002254305, REVEL 0.90, CADD 29.50, Uncertain significance, Transitory neonatal diabetes mellitus; Maturity-onset diabetes of the young; not
- H36P (p.His36Pro), gnomAD rs1468544724, Uncertain significance
- H36Q (p.His36Gln), ExAC rs757935183, TOPMed rs757935183, gnomAD rs757935183, REVEL 0.51, CADD 19.00, Likely benign
- H36R (p.His36Arg), rs1468544724, ClinGen CA379789969, ClinVar RCV003322278, gnomAD rs1468544724, REVEL 0.86, CADD 29.10, Uncertain significance, Hyperinsulinemic hypoglycemia, familial, 1
- H36Y (p.His36Tyr), rs1565001297, ClinGen CA379789975, ClinVar RCV003322282, ClinVar RCV005240746, REVEL 0.74, CADD 31.00, Uncertain significance, not specified; Hyperinsulinemic hypoglycemia, familial, 1
- V37A (p.Val37Ala), Ensembl rs1848799362
- V37I (p.Val37Ile), gnomAD rs1848799538, REVEL 0.59, CADD 24.60
- L39P (p.Leu39Pro), Ensembl rs865955550, REVEL 0.94, CADD 32.00
- L40I (p.Leu40Ile), gnomAD rs1462117805, REVEL 0.55, CADD 23.50
- L40R (p.Leu40Arg), rs1554949242, ClinGen CA379789899, ClinVar RCV000673351, ClinVar RCV001816681, REVEL 0.95, CADD 32.00, Conflicting interpretations, Transitory neonatal diabetes mellitus; Maturity-onset diabetes of the young; not
- L40V (p.Leu40Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F41S (p.Phe41Ser), rs2496929792, ClinGen CA379789885, ClinVar RCV003151531, ClinVar RCV004786882, Likely pathogenic, Hyperinsulinemic hypoglycemia, familial, 1
- I42V (p.Ile42Val), TOPMed rs1848798012, REVEL 0.64, CADD 22.80
- T43I (p.Thr43Ile), cosmic curated COSV10813
- F44L (p.Phe44Leu), Ensembl rs890699383, REVEL 0.63, CADD 24.30
- P45L (p.Pro45Leu), rs267606623, ClinGen CA254640, ClinVar RCV000009680, ClinVar RCV002512948, REVEL 0.82, CADD 26.60, Uncertain significance, not provided
- I46F (p.Ile46Phe), ExAC rs759639212, TOPMed rs759639212, gnomAD rs759639212, REVEL 0.66, CADD 32.00
- I46V (p.Ile46Val), ExAC rs759639212, TOPMed rs759639212, gnomAD rs759639212
- L47F (p.Leu47Phe), ExAC rs751811897, gnomAD rs751811897, REVEL 0.57, CADD 25.20
- L47P (p.Leu47Pro), Ensembl rs1051138725
- F48Y (p.Phe48Tyr), NCI-TCGA Cosmic COSV5685, cosmic curated COSV56851, Variant assessed as somatic; moderate impact.
- I49F (p.Ile49Phe), rs1554949196, ClinGen CA379789749, ClinVar RCV000671753, ClinVar RCV002051878, AlphaMissense 0.16, MetaLR 0.85, Likely pathogenic, Neonatal diabetes mellitus
- I49T (p.Ile49Thr), gnomAD rs1338924544, REVEL 0.82, CADD 32.00
- I49V (p.Ile49Val), rs1554949196, ClinGen CA379789751, ClinVar RCV002254146, ClinVar RCV002254147, REVEL 0.58, AlphaMissense 0.16, Conflicting interpretations, Diabetes mellitus, permanent neonatal 3; not provided; Transitory neonatal diabe
- W51* (p.Trp51Ter), rs1591928988, ClinGen CA379788703, ClinVar RCV000814291, ClinVar RCV002254319, CADD 37.00, Pathogenic
- W51R (p.Trp51Arg), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, Variant assessed as somatic; moderate impact.
- G52E (p.Gly52Glu), rs1404720025, NCI-TCGA Cosmic COSV5685, cosmic curated COSV56856, TOPMed rs1404720025, REVEL 0.83, CADD 26.30, Variant assessed as somatic; moderate impact.
- G52R (p.Gly52Arg), ExAC rs766663590, TOPMed rs766663590, gnomAD rs766663590, REVEL 0.74, CADD 24.80, Uncertain significance, Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familia
- S53G (p.Ser53Gly), rs2496919580, ClinGen CA379788653, ClinVar RCV002892095, REVEL 0.80, CADD 24.90, Uncertain significance, Inborn genetic diseases
- S53N (p.Ser53Asn), gnomAD rs1591928946, REVEL 0.72, CADD 23.30
- S53R (p.Ser53Arg), gnomAD rs1285560687, REVEL 0.65, CADD 16.80
- Q54* (p.Gln54Ter), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, Variant assessed as somatic; high impact.
- S55I (p.Ser55Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S55N (p.Ser55Asn), TOPMed rs1452808123, REVEL 0.59, CADD 23.70
- S56F (p.Ser56Phe), cosmic curated COSV10740
- K57N (p.Lys57Asn), ExAC rs750479324, gnomAD rs750479324, Uncertain significance, Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familia
- K57Q (p.Lys57Gln), TOPMed rs1848683310
- K57R (p.Lys57Arg), rs762919223, ClinGen CA5903953, ClinVar RCV000710374, ClinVar RCV001825409, REVEL 0.66, CADD 23.30, Uncertain significance, not provided; Maturity-onset diabetes of the young; Transitory neonatal diabetes
- V58M (p.Val58Met), gnomAD rs1285524167, REVEL 0.70, CADD 25.80
- H61R (p.His61Arg), Ensembl rs1848682183
- S63I (p.Ser63Ile), rs2496919339, ClinGen CA379788197, ClinVar RCV003577095, Uncertain significance, Maturity-onset diabetes of the young
- T64A (p.Thr64Ala), ExAC rs762341410, gnomAD rs762341410
- T64I (p.Thr64Ile), TOPMed rs1848681790, REVEL 0.71, CADD 24.60
- W65* (p.Trp65Ter), cosmic curated COSV56850, TOPMed rs1848681534
- L66P (p.Leu66Pro), TOPMed rs1295972947, gnomAD rs1295972947, REVEL 0.96, CADD 31.00
- H67R (p.His67Arg), gnomAD rs1282285867, REVEL 0.80, CADD 23.50
- H67Y (p.His67Tyr), Ensembl rs2133729039
- P69H (p.Pro69His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P69L (p.Pro69Leu), gnomAD rs1346510033, REVEL 0.89, CADD 28.90
- G70E (p.Gly70Glu), UniProt VAR 031352, Likely pathogenic, Hereditary hyperinsulinism
- G70R (p.Gly70Arg), rs764349043, ClinGen CA5903949, ClinVar RCV002224395, ClinVar RCV002487022, REVEL 0.89, CADD 27.90, Uncertain significance, not specified
- H71N (p.His71Asn), Ensembl rs1591928718
- N72D (p.Asn72Asp), rs2133728894, ClinGen CA379787908, ClinVar RCV001797879, Ensembl rs2133728894, AlphaMissense 0.37, MetaLR 0.89, Uncertain significance, not specified
- N72S (p.Asn72Ser), rs80356634, ClinGen CA340870, ClinVar RCV000009677, ClinVar RCV001089459, REVEL 0.61, CADD 23.30, Conflicting interpretations, not specified; Type 2 diabetes mellitus
- L73V (p.Leu73Val), TOPMed rs1324353873
- R74L (p.Arg74Leu), ExAC rs72559734, TOPMed rs72559734, gnomAD rs72559734, REVEL 0.94, CADD 27.50, Pathogenic, in HHF1
- R74Q (p.Arg74Gln), rs72559734, ClinGen CA5903946, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, REVEL 0.90, CADD 28.00, Pathogenic/Likely pathogenic, not provided; Familial hyperinsulinism; Hereditary hyperinsulinism
- R74W (p.Arg74Trp), rs201682634, ClinGen CA5903947, ClinVar RCV000409175, ClinVar RCV001203709, REVEL 0.98, CADD 32.00, Pathogenic/Likely pathogenic, ABCC8-related disorder; Hereditary hyperinsulinism; Diabetes mellitus, transient
- W75C (p.Trp75Cys), TOPMed rs1407794908, gnomAD rs1407794908, REVEL 0.93, CADD 31.00
- I76M (p.Ile76Met), ExAC rs773812588, gnomAD rs773812588, Likely benign
- L77R (p.Leu77Arg), Ensembl rs72559732
- L77V (p.Leu77Val), Ensembl rs72559733
- T78I (p.Thr78Ile), TOPMed rs1176679806, gnomAD rs1176679806, REVEL 0.79, CADD 27.20
- M80I (p.Met80Ile), TOPMed rs1242711631, gnomAD rs1242711631, REVEL 0.32, CADD 14.00
- M80R (p.Met80Arg), rs797045208, ClinGen CA277044, ClinVar RCV000192892, ClinVar RCV005042409, REVEL 0.56, CADD 23.50, Conflicting interpretations, Diabetes mellitus, transient neonatal, 2; Type 2 diabetes mellitus; Hyperinsulin
- M80V (p.Met80Val), TOPMed rs1848675735
- F83L (p.Phe83Leu), gnomAD rs1463898525, REVEL 0.63, CADD 16.10, Likely benign
- V84F (p.Val84Phe), ExAC rs775776658, TOPMed rs775776658, gnomAD rs775776658, REVEL 0.78, CADD 24.80, Likely pathogenic
- V84I (p.Val84Ile), rs775776658, ClinGen CA5903942, NCI-TCGA Cosmic COSV5685, cosmic curated COSV56856, REVEL 0.55, CADD 19.10, Conflicting interpretations, Monogenic diabetes; not provided; Hyperinsulinemic hypoglycemia, familial, 1
- V84L (p.Val84Leu), ExAC rs775776658, TOPMed rs775776658, gnomAD rs775776658, REVEL 0.64, CADD 20.70, Likely pathogenic
- V86A (p.Val86Ala), rs193929360, ClinGen CA341686, ClinVar RCV000020285, ClinVar RCV003137539, AlphaMissense 0.39, MetaLR 0.91, Conflicting interpretations, not provided
- V86G (p.Val86Gly), rs193929360, ClinGen CA340877, ClinVar RCV000009681, ClinVar RCV001089462, AlphaMissense 0.39, MetaLR 0.91, Pathogenic, Diabetes mellitus, permanent neonatal 3
- C87Y (p.Cys87Tyr), TOPMed rs1342950809
- E88D (p.Glu88Asp), cosmic curated COSV10610
- E88K (p.Glu88Lys), gnomAD rs1848673546, Uncertain significance, not provided
- I89M (p.Ile89Met), rs748024592, ClinGen CA379787377, ClinVar RCV003332029, REVEL 0.71, CADD 22.00, Uncertain significance, not specified
- I89T (p.Ile89Thr), TOPMed rs1429527957, gnomAD rs1429527957, REVEL 0.95, CADD 25.90
- I89V (p.Ile89Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A90V (p.Ala90Val), NCI-TCGA Cosmic COSV5685, cosmic curated COSV56856, Variant assessed as somatic; moderate impact.
- E91K (p.Glu91Lys), cosmic curated COSV56858
- E91Q (p.Glu91Gln), NCI-TCGA Cosmic COSV5685, REVEL 0.75, CADD 25.80, Variant assessed as somatic; moderate impact.
- G92C (p.Gly92Cys), NCI-TCGA Cosmic COSV5685, cosmic curated COSV56858, Variant assessed as somatic; moderate impact.
- G92S (p.Gly92Ser), ExAC rs780870376, TOPMed rs780870376, gnomAD rs780870376, REVEL 0.89, CADD 26.00, Uncertain significance, not provided; Hyperinsulinemic hypoglycemia, familial, 1
- I93T (p.Ile93Thr), ExAC rs758604661, gnomAD rs758604661, REVEL 0.67, CADD 24.00, Uncertain significance, Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familia
- I93V (p.Ile93Val), TOPMed rs1848672468
- S95Y (p.Ser95Tyr), TOPMed rs1056079916, REVEL 0.78, CADD 27.70
- G97E (p.Gly97Glu), cosmic curated COSV56850
- G97R (p.Gly97Arg), rs1405170371, ClinGen CA379787027, NCI-TCGA Cosmic COSV5685, cosmic curated COSV56854, REVEL 0.55, CADD 24.40, Uncertain significance, Inborn genetic diseases
- V98M (p.Val98Met), cosmic curated COSV56854
- E100* (p.Glu100Ter), cosmic curated COSV10645, CADD 36.00, Uncertain significance
- E100D (p.Glu100Asp), ExAC rs753151571, gnomAD rs753151571, REVEL 0.28, CADD 2.56, Uncertain significance
- E100K (p.Glu100Lys), rs200687571, ClinGen CA5903914, NCI-TCGA Cosmic COSV5684, cosmic curated COSV56848, REVEL 0.29, CADD 14.30, Conflicting interpretations, not provided; Leucine-induced hypoglycemia; Diabetes mellitus, permanent neonata
- H102N (p.His102Asn), cosmic curated COSV10021
- H102Q (p.His102Gln), ExAC rs759952645, gnomAD rs759952645, REVEL 0.30, CADD 17.80, Likely benign
- H102Y (p.His102Tyr), gnomAD rs1310538698, REVEL 0.39, CADD 17.60
- H103Y (p.His103Tyr), rs751209734, ClinGen CA5903910, NCI-TCGA Cosmic COSV5684, cosmic curated COSV56848, REVEL 0.66, CADD 23.60, Uncertain significance, not specified
- L104P (p.Leu104Pro), Ensembl rs1848405429, REVEL 0.73, CADD 23.80
- L104V (p.Leu104Val), rs10400391, UniProt VAR 029777, Ensembl rs10400391, AlphaMissense 0.26, MetaLR 0.89
- H105Q (p.His105Gln), Ensembl rs1848404808, REVEL 0.80, CADD 19.80, Uncertain significance, Hereditary hyperinsulinism
- H105R (p.His105Arg), Ensembl rs1848404950, REVEL 0.92, CADD 23.00
- H105Y (p.His105Tyr), rs766068851, ClinGen CA5903909, ClinVar RCV001817803, ClinVar RCV005040401, REVEL 0.78, CADD 25.60, Conflicting interpretations, not provided; Diabetes mellitus, transient neonatal, 2; Diabetes mellitus, perma
- Y107C (p.Tyr107Cys), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, REVEL 0.81, AlphaMissense 0.07, Variant assessed as somatic; moderate impact.
- M108V (p.Met108Val), ExAC rs772737291, gnomAD rs772737291, REVEL 0.51, CADD 18.40, Uncertain significance, Hereditary hyperinsulinism
- P109L (p.Pro109Leu), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, Variant assessed as somatic; moderate impact.
- A110V (p.Ala110Val), TOPMed rs894014049, REVEL 0.69, AlphaMissense 0.77, Uncertain significance, not provided
- G111E (p.Gly111Glu), rs2133711374, ClinGen CA379784382, ClinVar RCV002042485, Ensembl rs2133711374, AlphaMissense 0.92, MetaLR 0.85, Likely pathogenic, not provided
- G111R (p.Gly111Arg), rs761749884, ClinGen CA277230, ClinVar RCV000193936, ClinVar RCV001068772, REVEL 0.64, CADD 21.80, Pathogenic/Likely pathogenic, Diabetes mellitus, transient neonatal, 2; Type 2 diabetes mellitus; Hyperinsulin
- G111W (p.Gly111Trp), cosmic curated COSV56857
- M112V (p.Met112Val), ExAC rs776487104, gnomAD rs776487104, REVEL 0.46, AlphaMissense 0.45
- A113V (p.Ala113Val), rs2133711315, ClinGen CA379784330, cosmic curated COSV56847, ClinVar RCV001817966, REVEL 0.75, CADD 24.80, Conflicting interpretations, Hereditary hyperinsulinism; Type 2 diabetes mellitus; Diabetes mellitus, transie
- M115V (p.Met115Val), rs146695489, ClinGen CA5903905, ClinVar RCV001105013, ClinVar RCV001869139, REVEL 0.71, AlphaMissense 0.17, Conflicting interpretations, not provided; not specified; Hyperinsulinemic hypoglycemia, familial, 1
- A116P (p.Ala116Pro), rs72559731, UniProt VAR 031356, Ensembl rs72559731, AlphaMissense 0.99, MetaLR 0.94, Pathogenic, in HHF1
- A117G (p.Ala117Gly), ExAC rs746836780, gnomAD rs746836780, REVEL 0.33, CADD 22.20
- A117T (p.Ala117Thr), TOPMed rs1848402786
- A117V (p.Ala117Val), cosmic curated COSV10965, ExAC rs746836780, gnomAD rs746836780
- V118I (p.Val118Ile), ESP rs144641450, TOPMed rs144641450
- T119I (p.Thr119Ile), cosmic curated COSV56847
- T119N (p.Thr119Asn), ExAC rs749506839, gnomAD rs749506839, REVEL 0.75, AlphaMissense 0.33
- S120F (p.Ser120Phe), rs1222549831, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10021, gnomAD rs1222549831, REVEL 0.78, AlphaMissense 0.13, Variant assessed as somatic; moderate impact.
Public ABCC8 analysis runs
- ABCC8 analysis run — ABCC8 (2,466 variants) — completed 2026-08-18