GCK (Hexokinase-4) variants and mutations
GCK (also known as Hexokinase-4) is a human protein-coding gene encoding a hexokinase-4 protein. It sets the glucose threshold for insulin secretion in pancreatic beta cells and controls hepatic glucose phosphorylation after meals. Heterozygous loss-of-function variants cause GCK-MODY, stronger loss can cause neonatal diabetes, and activating variants can cause hyperinsulinemic hypoglycemia. This analysis covers 1,184 GCK variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes Alzheimer disease, Parkinson disease, and neurodegenerative disease. Example GCK variants include M1I, M1L, and D3Y.
Variant analysis overview
- Gene: GCK
- Protein: Hexokinase-4
- UniProt accession: P35557
- Organism: Homo sapiens
- Variants analyzed: 1184
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 948 unspecified-consequence records; 2 stop lost; 86 synonymous variants; 10 frameshift variants; 123 missense variants; 3 splice-region variants; 3 in-frame deletions; 2 stop-gained variants; 6 substitution
- Prediction scores: 894 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Alzheimer disease, Parkinson disease, neurodegenerative disease, lysosomal storage disease, multiple sclerosis, autoimmune disorder of central nervous system, gout, rheumatoid arthritis, post-traumatic stress disorder, cholelithiasis, physical activity, alcohol drinking.
Protein structure and variant hotspots
- Protein features: 1 domains; 11 binding sites.
- Structural context: 1,132 variants have structural context.
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 GCK variants
Examples include M1I, M1L, D3Y, D4G, D4N, R5G, R5K, A6T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2484626549, ClinGen CA367358349, ClinVar RCV003481519, Uncertain significance, Monogenic diabetes
- M1L (p.Met1Leu), rs2484626558, ClinGen CA367358357, ClinVar RCV003230246, Likely benign, Hyperinsulinemic hypoglycemia, familial, 3
- D3Y (p.Asp3Tyr), NCI-TCGA Cosmic COSV6788, cosmic curated COSV67885, Variant assessed as somatic; moderate impact.
- D4G (p.Asp4Gly), Ensembl rs2128834778
- D4N (p.Asp4Asn), rs202091228, ClinGen CA4239800, ClinVar RCV001164411, ClinVar RCV001164412, REVEL 0.31, CADD 14.40, Uncertain significance, Monogenic diabetes
- R5G (p.Arg5Gly), gnomAD rs1212859987, REVEL 0.52, CADD 20.20
- R5K (p.Arg5Lys), TOPMed rs1339026807, gnomAD rs1339026807, REVEL 0.50, CADD 17.90
- A6T (p.Ala6Thr), rs754792276, ClinGen CA4239799, ClinVar RCV001769217, ExAC rs754792276, REVEL 0.42, CADD 17.00, Uncertain significance, not provided
- A6V (p.Ala6Val), TOPMed rs1344038635, gnomAD rs1344038635, REVEL 0.55, CADD 22.40, Uncertain significance, Monogenic diabetes
- R7G (p.Arg7Gly), cosmic curated COSV67884
- R7K (p.Arg7Lys), cosmic curated COSV67886, ExAC rs746248882, gnomAD rs746248882, CADD 1.89
- E9* (p.Glu9Ter), rs1131691483, ClinGen CA367358148, ClinVar RCV000494362, ClinVar RCV002463682, AlphaMissense 0.20, MetaLR 0.73, Pathogenic
- E9K (p.Glu9Lys), NCI-TCGA Cosmic COSV6788, cosmic curated COSV67884, Variant assessed as somatic; moderate impact.
- E9Q (p.Glu9Gln), Ensembl rs1131691483, REVEL 0.49, AlphaMissense 0.20, Pathogenic
- A10T (p.Ala10Thr), rs1265357992, ClinGen CA367358129, NCI-TCGA Cosmic COSV6788, cosmic curated COSV67885, CADD 1.86, Uncertain significance, Maturity-onset diabetes of the young type 2; Hyperinsulinemic hypoglycemia, fami
- A10V (p.Ala10Val), NCI-TCGA Cosmic COSV6788, cosmic curated COSV67883, Variant assessed as somatic; moderate impact.
- A11G (p.Ala11Gly), cosmic curated COSV67886
- A11P (p.Ala11Pro), 1000Genomes rs116093166, ESP rs116093166, ExAC rs116093166, TOPMed rs116093166, Benign
- A11T (p.Ala11Thr), rs116093166, ClinGen CA152952, cosmic curated COSV67883, ClinVar RCV000117128, REVEL 0.31, CADD 4.69, Benign, Monogenic diabetes
- A11V (p.Ala11Val), ExAC rs749422860, TOPMed rs749422860, gnomAD rs749422860, REVEL 0.44, CADD 22.70
- K12R (p.Lys12Arg), rs777958777, ClinGen CA4239795, ClinVar RCV001252995, ExAC rs777958777, REVEL 0.63, CADD 24.60, Uncertain significance, Maturity-onset diabetes of the young type 2
- K13N (p.Lys13Asn), ExAC rs756232246, TOPMed rs756232246, gnomAD rs756232246
- K13Q (p.Lys13Gln), cosmic curated COSV10133
- E14D (p.Glu14Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E14K (p.Glu14Lys), NCI-TCGA Cosmic COSV6788, cosmic curated COSV67883, REVEL 0.61, CADD 23.10, Variant assessed as somatic; moderate impact.
- E14Q (p.Glu14Gln), TOPMed rs1454187488, gnomAD rs1454187488, REVEL 0.60, CADD 23.40, Uncertain significance, Monogenic diabetes
- E14V (p.Glu14Val), Ensembl rs2096324286
- K15R (p.Lys15Arg), rs2484626373, ClinGen CA367357957, ClinVar RCV003035762, Uncertain significance, not provided
- V16E (p.Val16Glu), cosmic curated COSV10886, UniProt VAR 079430, Uncertain significance, Monogenic diabetes
- V16G (p.Val16Gly), Ensembl rs1583604898, REVEL 0.80, CADD 22.40
- E17A (p.Glu17Ala), cosmic curated COSV10059
- E17Q (p.Glu17Gln), gnomAD rs1184614923, REVEL 0.58, CADD 19.40, Uncertain significance, Maturity-onset diabetes of the young type 2; Permanent neonatal diabetes mellitu
- E17G (p.Glu17Gly), Ensembl rs113565983
- Q18* (p.Gln18Ter), rs1300199281, ClinGen CA367403853, ClinVar RCV002227421, TOPMed rs1300199281, AlphaMissense 0.08, MetaLR 0.91, Likely pathogenic
- Q18H (p.Gln18His), rs2096283329, ClinGen CA367403838, ClinVar RCV002222321, ClinVar RCV004990746, REVEL 0.68, CADD 22.40, Uncertain significance, Monogenic diabetes
- Q18K (p.Gln18Lys), rs1300199281, TOPMed rs1300199281, gnomAD rs1300199281, REVEL 0.64, AlphaMissense 0.08, Likely pathogenic
- Q18R (p.Gln18Arg), ExAC rs765737449, TOPMed rs765737449, gnomAD rs765737449, REVEL 0.69, CADD 22.00, Uncertain significance, Maturity-onset diabetes of the young type 2; Permanent neonatal diabetes mellitu
- I19M (p.Ile19Met), rs193922308, ClinGen CA213804, ClinVar RCV000029893, TOPMed rs193922308, AlphaMissense 0.17, MetaLR 0.96, Likely pathogenic, Maturity-onset diabetes of the young type 2
- I19N (p.Ile19Asn), rs2484540549, cosmic curated COSV10606, ClinGen CA367403826, ClinVar RCV003037224, REVEL 0.86, CADD 27.70, Pathogenic, Monogenic diabetes
- L20P (p.Leu20Pro), rs2484540522, ClinGen CA367403809, ClinVar RCV003231847, UniProt VAR 079432, Likely pathogenic, not provided
- A21V (p.Ala21Val), cosmic curated COSV61753
- E22G (p.Glu22Gly), TOPMed rs2096283320, REVEL 0.80, CADD 24.10
- E22Q (p.Glu22Gln), cosmic curated COSV61754, REVEL 0.62, CADD 22.20
- Q24* (p.Gln24Ter), rs1281712444, ClinGen CA367403752, ClinVar RCV000992060, ClinVar RCV002363516, CADD 37.00, Pathogenic
- Q24H (p.Gln24His), Ensembl rs2096283310, NCI-TCGA Cosmic COSV6175, cosmic curated COSV61752, Variant assessed as somatic; moderate impact.
- L25Q (p.Leu25Gln), rs193922325, ClinGen CA16609255, ClinVar RCV000445551, Ensembl rs193922325, REVEL 0.92, AlphaMissense 0.73, Uncertain significance, Monogenic diabetes
- L25R (p.Leu25Arg), rs193922325, ClinGen CA213838, ClinVar RCV000029913, ClinVar RCV002464075, AlphaMissense 0.73, MetaLR 0.97, Conflicting interpretations, Maturity-onset diabetes of the young; not provided; Maturity-onset diabetes of t
- Q26* (p.Gln26Ter), rs193922329, ClinGen CA213850, ClinVar RCV000029919, ClinVar RCV000255007, AlphaMissense 0.10, MetaLR 0.69, Pathogenic
- Q26R (p.Gln26Arg), TOPMed rs2096283296
- E27K (p.Glu27Lys), cosmic curated COSV61755, REVEL 0.41, CADD 20.60, Uncertain significance, Maturity-onset diabetes of the young; not provided
- E27Q (p.Glu27Gln), Ensembl rs2096283280
- E28K (p.Glu28Lys), rs2128823215, ClinGen CA367403690, NCI-TCGA Cosmic COSV6175, cosmic curated COSV61753, REVEL 0.71, CADD 22.00, Uncertain significance, Maturity-onset diabetes of the young; not provided
- E28V (p.Glu28Val), cosmic curated COSV61753
- D29E (p.Asp29Glu), cosmic curated COSV61755
- D29G (p.Asp29Gly), cosmic curated COSV61755
- D29Y (p.Asp29Tyr), rs2484540304, ClinGen CA367403666, ClinVar RCV002475242, Conflicting interpretations, not provided; Maturity-onset diabetes of the young type 2
- L30M (p.Leu30Met), cosmic curated COSV10524
- L30P (p.Leu30Pro), rs876661320, ClinGen CA10581225, ClinVar RCV000223803, ClinVar RCV003556284, AlphaMissense 0.98, MetaLR 0.99, Likely pathogenic, Monogenic diabetes
- K31N (p.Lys31Asn), gnomAD rs1194717950, REVEL 0.47, CADD 16.90
- K31R (p.Lys31Arg), TOPMed rs2096283274, gnomAD rs2096283274, REVEL 0.48, CADD 21.60
- V33A (p.Val33Ala), rs1554335954, ClinGen CA367403604, ClinVar RCV000711790, ClinVar RCV002285408, AlphaMissense 0.73, MetaLR 0.94, Likely pathogenic, Monogenic diabetes
- V33E (p.Val33Glu), rs1554335954, ClinGen CA367403606, ClinVar RCV000502611, ClinVar RCV002383967, AlphaMissense 0.73, MetaLR 0.94, Uncertain significance, Monogenic diabetes
- V33G (p.Val33Gly), rs1554335954, ClinGen CA367403603, ClinVar RCV002464672, Ensembl rs1554335954, AlphaMissense 0.73, MetaLR 0.94, Uncertain significance, Monogenic diabetes
- M34I (p.Met34Ile), rs2096283252, ClinGen CA367403586, ClinVar RCV002227430, ClinVar RCV004729107, AlphaMissense 0.86, MetaLR 0.95, Conflicting interpretations, not provided; Maturity-onset diabetes of the young type 2
- R35* (p.Arg35Ter), rs193922259, ClinGen CA213705, ClinVar RCV000029834, ClinVar RCV002463995, Likely pathogenic
- R35K (p.Arg35Lys), gnomAD rs1461524859
- R36P (p.Arg36Pro), rs193922261, ClinGen CA213709, ClinVar RCV000029836, ClinVar RCV006461227, AlphaMissense 0.14, MetaLR 0.95, Conflicting interpretations, not provided; Maturity-onset diabetes of the young type 2
- R36Q (p.Arg36Gln), rs193922261, ClinGen CA367403564, cosmic curated COSV61754, ClinVar RCV001249065, REVEL 0.83, AlphaMissense 0.16, Uncertain significance, Monogenic diabetes
- R36W (p.Arg36Trp), rs762263694, ClinGen CA4239720, NCI-TCGA Cosmic COSV6175, cosmic curated COSV61752, REVEL 0.91, CADD 25.40, Pathogenic, Monogenic diabetes
- M37K (p.Met37Lys), rs2484540129, ClinGen CA367403546, ClinVar RCV003494030, Uncertain significance, Monogenic diabetes
- M37R (p.Met37Arg), rs2484540129, ClinGen CA367403541, ClinVar RCV003326083, Pathogenic, Monogenic diabetes
- M37T (p.Met37Thr), rs2484540129, cosmic curated COSV61755, ClinGen CA367403544, ClinVar RCV003481518, Likely pathogenic, Monogenic diabetes
- M37V (p.Met37Val), rs2484540140, ClinGen CA367403551, ClinVar RCV003445456, Likely pathogenic, Monogenic diabetes
- Q38* (p.Gln38Ter), rs878853246, ClinGen CA10581556, ClinVar RCV000225041, ClinVar RCV002464012, Pathogenic
- Q38L (p.Gln38Leu), rs1064794268, cosmic curated COSV10817, ClinGen CA367403522, ClinVar RCV003494025, AlphaMissense 0.92, MetaLR 0.96, Likely pathogenic, Monogenic diabetes
- Q38P (p.Gln38Pro), rs1064794268, ClinGen CA16618475, ClinVar RCV000480480, ClinVar RCV000754804, REVEL 0.89, AlphaMissense 0.92, Pathogenic, Monogenic diabetes
- K39E (p.Lys39Glu), cosmic curated COSV10059
- E40* (p.Glu40Ter), rs794727236, ClinGen CA367403485, ClinVar RCV003991166, AlphaMissense 0.95, MetaLR 0.98, Pathogenic, in PNDM1
- E40K (p.Glu40Lys), rs794727236, ClinGen CA201503, ClinVar RCV000175536, ClinVar RCV003388832, AlphaMissense 0.95, MetaLR 0.98, Pathogenic, Monogenic diabetes
- M41R (p.Met41Arg), rs1057524906, ClinGen CA367403469, ClinVar RCV002285551, AlphaMissense 0.96, MetaLR 0.98, Likely pathogenic, Maturity-onset diabetes of the young type 2
- M41T (p.Met41Thr), rs1057524906, ClinGen CA16609270, ClinVar RCV000445500, ClinVar RCV000992041, AlphaMissense 0.96, MetaLR 0.98, Conflicting interpretations, Monogenic diabetes; not provided
- M41V (p.Met41Val), rs1583604693, ClinGen CA367403472, ClinVar RCV000992040, ClinVar RCV002464351, REVEL 0.96, AlphaMissense 0.94, Conflicting interpretations, Maturity-onset diabetes of the young; not provided
- D42A (p.Asp42Ala), gnomAD rs866774967, REVEL 0.53, CADD 21.40
- D42G (p.Asp42Gly), gnomAD rs866774967
- D42H (p.Asp42His), rs1562719786, ClinGen CA367403461, ClinVar RCV000710053, ClinVar RCV002464294, REVEL 0.66, AlphaMissense 0.27, Uncertain significance/Uncertain risk allele, Maturity-onset diabetes of the young; not provided
- R43C (p.Arg43Cys), rs1486280029, ClinGen CA367403451, NCI-TCGA Cosmic COSV6175, cosmic curated COSV61753, REVEL 0.92, AlphaMissense 0.55, Pathogenic, Monogenic diabetes
- R43H (p.Arg43His), rs764232985, ClinGen CA4239718, ClinVar RCV000445457, ClinVar RCV000711763, REVEL 0.82, AlphaMissense 0.15, Pathogenic, Monogenic diabetes
- R43P (p.Arg43Pro), rs764232985, ClinGen CA367403448, ClinVar RCV000711764, ExAC rs764232985, AlphaMissense 0.15, MetaLR 0.95, Likely pathogenic, not provided
- R43S (p.Arg43Ser), rs1486280029, ClinGen CA367403453, cosmic curated COSV61754, ClinVar RCV000711760, AlphaMissense 0.55, MetaLR 0.94, Pathogenic/Likely pathogenic, not provided
- G44C (p.Gly44Cys), rs267601516, ClinGen CA367403443, ClinVar RCV003230884, ClinVar RCV003420621, REVEL 0.97, CADD 26.60, Conflicting interpretations, not provided; GCK-related disorder; not specified
- G44D (p.Gly44Asp), rs193922279, ClinGen CA213753, ClinVar RCV000029859, ClinVar RCV001659731, REVEL 0.99, CADD 25.60, Likely pathogenic, not provided; Maturity-onset diabetes of the young type 2
- G44S (p.Gly44Ser), rs267601516, ClinGen CA157920006, cosmic curated COSV61752, ClinVar RCV000992045, REVEL 0.96, CADD 25.90, Pathogenic/Likely pathogenic, Hyperinsulinemic hypoglycemia, familial, 3; Type 2 diabetes mellitus; Permanent
- L45P (p.Leu45Pro), rs1131691598, ClinGen CA367403437, ClinVar RCV000493595, ClinVar RCV002465692, REVEL 0.99, CADD 28.30, Conflicting interpretations, not provided; Maturity-onset diabetes of the young; not specified
- L45Q (p.Leu45Gln), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61755, Variant assessed as somatic; moderate impact.
- R46G (p.Arg46Gly), NCI-TCGA TCGA novel, Uncertain significance, not specified
- R46K (p.Arg46Lys), rs1064796993, ClinGen CA367403428, ClinVar RCV002465951, gnomAD rs1064796993, REVEL 0.40, CADD 9.97, Benign, Maturity-onset diabetes of the young
- R46M (p.Arg46Met), rs1064796993, ClinGen CA16618474, ClinVar RCV000479996, ClinVar RCV002285338, REVEL 0.74, CADD 16.10, Conflicting interpretations, not provided; Maturity-onset diabetes of the young type 2
- E48K (p.Glu48Lys), rs759514960, ClinGen CA4239714, ClinVar RCV001730073, ClinVar RCV003331193, REVEL 0.70, AlphaMissense 0.34, Likely benign, Monogenic diabetes
- T49I (p.Thr49Ile), rs193922286, ClinGen CA367403399, ClinVar RCV002047952, Ensembl rs193922286, AlphaMissense 0.21, MetaLR 0.97, Conflicting interpretations, not provided
- T49N (p.Thr49Asn), rs193922286, ClinGen CA213765, ClinVar RCV000029867, ClinVar RCV003325948, AlphaMissense 0.21, MetaLR 0.97, Likely pathogenic, Monogenic diabetes
- T49S (p.Thr49Ser), rs193922286, ClinGen CA367403400, ClinVar RCV003018951, AlphaMissense 0.21, MetaLR 0.97, Uncertain significance, not provided
- H50D (p.His50Asp), UniProt VAR 079437, Pathogenic, in PNDM1
- H50L (p.His50Leu), rs2484539875, ClinGen CA367403390, ClinVar RCV002289503, Uncertain significance, Maturity-onset diabetes of the young type 2
- H50Y (p.His50Tyr), rs1562719705, ClinGen CA367403394, ClinVar RCV000778070, ClinVar RCV001816832, AlphaMissense 0.38, MetaLR 0.95, Pathogenic/Likely pathogenic, Maturity-onset diabetes of the young type 2; Maturity-onset diabetes of the youn
- H50fsX, rs886041690, Pathogenic
- E51* (p.Glu51Ter), rs2096283124, ClinGen CA367403382, ClinVar RCV002392406, ClinVar RCV005645388, AlphaMissense 0.08, MetaLR 0.84, Pathogenic
- E51G (p.Glu51Gly), gnomAD rs1334992248, REVEL 0.42, CADD 22.40
- E51K (p.Glu51Lys), gnomAD rs2096283124, REVEL 0.30, AlphaMissense 0.08
- E51Q (p.Glu51Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E52K (p.Glu52Lys), TOPMed rs2096283117, REVEL 0.63, CADD 21.90
- A53S (p.Ala53Ser), UniProt VAR 010585, Uncertain significance, Monogenic diabetes
- A53V (p.Ala53Val), rs2128823130, ClinGen CA367403352, ClinVar RCV001817947, ClinVar RCV002285503, REVEL 0.94, CADD 33.00, Pathogenic, Monogenic diabetes
- S54N (p.Ser54Asn), TOPMed rs1386137950, gnomAD rs1386137950, REVEL 0.42, AlphaMissense 0.99, Uncertain significance, not provided
- S54R (p.Ser54Arg), ExAC rs749097393, gnomAD rs749097393, cosmic curated COSV10606, REVEL 0.71, CADD 17.80, Likely pathogenic, Monogenic diabetes
- K56R (p.Lys56Arg), Ensembl rs2096283096, REVEL 0.85, AlphaMissense 0.12
- K56T (p.Lys56Thr), rs2096283096, ClinGen CA367403326, ClinVar RCV002475236, ClinVar RCV003479431, AlphaMissense 0.12, MetaLR 0.94, Likely pathogenic, Monogenic diabetes
- M57I (p.Met57Ile), rs1057520109, ClinGen CA16618473, ClinVar RCV000479407, ClinVar RCV002402377, AlphaMissense 0.99, MetaLR 0.98, Pathogenic, Monogenic diabetes
- M57K (p.Met57Lys), rs2484539759, ClinGen CA367403317, ClinVar RCV003482698, ClinVar RCV005402037, REVEL 0.98, AlphaMissense 0.92, Likely pathogenic, Monogenic diabetes
- P59A (p.Pro59Ala), rs193922287, ClinGen CA367403309, ClinVar RCV001837096, ExAC rs193922287, AlphaMissense 0.61, MetaLR 0.98, Conflicting interpretations, not provided
- P59S (p.Pro59Ser), rs193922287, ClinGen CA213767, ClinVar RCV000029868, ClinVar RCV000518012, REVEL 0.96, AlphaMissense 0.47, Pathogenic/Likely pathogenic, not provided; Maturity-onset diabetes of the young type 2
- T60I (p.Thr60Ile), rs747783371, ClinGen CA4239709, ClinVar RCV001844458, ClinVar RCV002406905, REVEL 0.98, AlphaMissense 0.12, Pathogenic, Monogenic diabetes
- T60P (p.Thr60Pro), Ensembl rs1583604490, REVEL 0.98, CADD 28.20
- Y61* (p.Tyr61Ter), rs780612692, ClinGen CA367403288, ClinVar RCV000987868, ClinVar RCV002409317, CADD 33.00, Pathogenic, in MODY2
- Y61N (p.Tyr61Asn), rs2128823113, ClinGen CA367403298, ClinVar RCV001955981, Ensembl rs2128823113, AlphaMissense 0.89, MetaLR 0.96, Uncertain significance, not provided
- Y61S (p.Tyr61Ser), UniProt VAR 079439, Pathogenic, in MODY2
- V62A (p.Val62Ala), rs1444739794, ClinGen CA367403278, ClinVar RCV000711769, ClinVar RCV003480800, REVEL 0.97, AlphaMissense 0.06, Pathogenic, Monogenic diabetes
- V62M (p.Val62Met), rs1064793998, ClinGen CA16618472, ClinVar RCV000481874, ClinVar RCV000754817, REVEL 0.97, CADD 26.10, Pathogenic, Monogenic diabetes
- R63C (p.Arg63Cys), rs754479025, ClinGen CA4239707, NCI-TCGA Cosmic COSV6175, cosmic curated COSV61754, REVEL 0.52, CADD 23.00, Uncertain significance/Uncertain risk allele, not provided; not specified; Maturity-onset diabetes of the young
- R63H (p.Arg63His), rs746444094, ClinGen CA4239706, NCI-TCGA Cosmic COSV6175, cosmic curated COSV61752, REVEL 0.84, AlphaMissense 0.19, Uncertain significance, not provided
- R63L (p.Arg63Leu), rs746444094, ClinGen CA367403268, ClinVar RCV002022599, ExAC rs746444094, AlphaMissense 0.19, MetaLR 0.95, Uncertain significance, not provided
- S64F (p.Ser64Phe), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61754, Variant assessed as somatic; moderate impact.
- T65I (p.Thr65Ile), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61754, UniProt VAR 078243, REVEL 0.82, CADD 22.80, Pathogenic, in HHF3
- P66S (p.Pro66Ser), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61755, Variant assessed as somatic; moderate impact.
- E67G (p.Glu67Gly), Ensembl rs1562719618
- G68D (p.Gly68Asp), rs373418736, ClinGen CA157919943, ClinVar RCV001248984, ClinVar RCV003481036, REVEL 0.98, CADD 26.10, Likely benign, Monogenic diabetes
- G68S (p.Gly68Ser), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61755, Variant assessed as somatic; moderate impact., in MODY2
- E70K (p.Glu70Lys), rs2128823091, ClinGen CA367403203, ClinVar RCV002227431, ClinVar RCV002473357, AlphaMissense 0.93, MetaLR 0.99, Pathogenic/Likely pathogenic, Maturity-onset diabetes of the young type 2; Maturity-onset diabetes of the youn
- E70Q (p.Glu70Gln), rs2128823091, ClinGen CA367403201, ClinVar RCV003330064, ClinVar RCV005061278, AlphaMissense 0.93, MetaLR 0.99, Conflicting interpretations, Maturity-onset diabetes of the young; not specified
- G72E (p.Gly72Glu), rs2128822720, ClinGen CA367403110, ClinVar RCV001822813, Ensembl rs2128822720, AlphaMissense 0.99, MetaLR 0.99, Conflicting interpretations, not provided
- G72R (p.Gly72Arg), rs193922289, ClinGen CA213771, ClinVar RCV000029872, ClinVar RCV000255585, REVEL 0.99, CADD 26.80, Pathogenic, Monogenic diabetes
- D73E (p.Asp73Glu), rs2096281841, ClinGen CA367403096, ClinVar RCV003394466, Uncertain significance, GCK-related disorder
- F74I (p.Phe74Ile), cosmic curated COSV61753
- L75F (p.Leu75Phe), cosmic curated COSV10466
- S76A (p.Ser76Ala), cosmic curated COSV10649
- S76Y (p.Ser76Tyr), rs2484536033, ClinGen CA367403060, ClinVar RCV003482699, Uncertain significance, not provided
- L77P (p.Leu77Pro), rs2096281827, ClinGen CA367403052, ClinVar RCV001289436, ClinVar RCV006454725, AlphaMissense 1.00, MetaLR 0.99, Likely pathogenic, Monogenic diabetes
- D78E (p.Asp78Glu), rs1219798321, ClinGen CA367403036, ClinVar RCV002475241, UniProt VAR 079442, Uncertain significance, Monogenic diabetes
- D78Y (p.Asp78Tyr), rs2484535997, ClinGen CA367403044, ClinVar RCV003224686, ClinVar RCV004798038, Pathogenic, Monogenic diabetes
- D78N (p.Asp78Asn), rs867232360, []
- L79M (p.Leu79Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G80A (p.Gly80Ala), UniProt VAR 003694, Pathogenic, in MODY2
- G80D (p.Gly80Asp), UniProt VAR 079443, Likely pathogenic, Maturity-onset diabetes of the young type 2
- G80S (p.Gly80Ser), rs1554335761, ClinGen CA367403023, ClinVar RCV000519805, UniProt VAR 003695, AlphaMissense 0.99, MetaLR 0.99, Likely pathogenic, not provided
- G80V (p.Gly80Val), cosmic curated COSV61755, Likely pathogenic, not provided
- G81D (p.Gly81Asp), rs866182415, ClinGen CA157919284, ClinVar RCV004556149, Ensembl rs866182415, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, Maturity-onset diabetes of the young type 2
- T82I (p.Thr82Ile), rs2484535943, ClinGen CA367402995, ClinVar RCV002308507, UniProt VAR 079444, Likely pathogenic, Maturity-onset diabetes of the young type 2
- N83D (p.Asn83Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F84S (p.Phe84Ser), rs2128822702, ClinGen CA367402973, ClinVar RCV002049532, Ensembl rs2128822702, AlphaMissense 0.99, MetaLR 0.98, Uncertain significance, not provided
- F84V (p.Phe84Val), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61754, Variant assessed as somatic; moderate impact.
- R85S (p.Arg85Ser), rs1554335758, ClinGen CA367402958, ClinVar RCV000625634, ClinVar RCV002465739, AlphaMissense 0.99, MetaLR 0.99, Uncertain risk allele, Maturity-onset diabetes of the young
- R85W (p.Arg85Trp), rs193922290, ClinGen CA213773, ClinVar RCV000029873, ClinVar RCV002465491, AlphaMissense 0.94, MetaLR 0.99, Conflicting interpretations, Maturity-onset diabetes of the young; Maturity-onset diabetes of the young type
- K90N (p.Lys90Asn), cosmic curated COSV61754
- K90T (p.Lys90Thr), rs2128822695, ClinGen CA367402900, ClinVar RCV002221403, Ensembl rs2128822695, AlphaMissense 0.21, MetaLR 0.93, Likely pathogenic, Hyperinsulinemic hypoglycemia, familial, 3
- V91L (p.Val91Leu), rs2484535683, ClinVar RCV000017528, UniProt VAR 078244, Pathogenic, not provided
- G92E (p.Gly92Glu), NCI-TCGA Cosmic COSV6175, cosmic curated COSV61753, REVEL 0.64, AlphaMissense 0.68, Variant assessed as somatic; moderate impact.
- G92V (p.Gly92Val), cosmic curated COSV61755
- E93A (p.Glu93Ala), rs2484535641, ClinGen CA367402868, ClinVar RCV002468458, Uncertain significance, Hyperinsulinemic hypoglycemia, familial, 3; Maturity-onset diabetes of the young
- E95G (p.Glu95Gly), ExAC rs755129550
- E96* (p.Glu96Ter), rs2096281776, ClinGen CA367402838, ClinVar RCV001289437, ClinVar RCV002465863, Pathogenic
- E96K (p.Glu96Lys), cosmic curated COSV61756, REVEL 0.38, CADD 18.30
- G97E (p.Gly97Glu), gnomAD rs1199862382, REVEL 0.61, CADD 21.10
- G97R (p.Gly97Arg), ExAC rs751666458, TOPMed rs751666458, gnomAD rs751666458, REVEL 0.44, CADD 19.30
- Q98* (p.Gln98Ter), rs2484535560, ClinGen CA367402818, ClinVar RCV003893758, ClinVar RCV005430867, Pathogenic
- Q98H (p.Gln98His), cosmic curated COSV10744
- W99* (p.Trp99Ter), rs2484535524, cosmic curated COSV61755, ClinGen CA367402804, ClinVar RCV002285555, Pathogenic, in HHF3
- W99C (p.Trp99Cys), UniProt VAR 078245, Pathogenic, in HHF3
- W99R (p.Trp99Arg), rs1554335751, ClinGen CA367402811, ClinVar RCV000518344, ClinVar RCV003988850, AlphaMissense 0.62, MetaLR 0.92, Conflicting interpretations, not provided; Maturity-onset diabetes of the young type 2
- S100G (p.Ser100Gly), TOPMed rs2096281753, REVEL 0.49, CADD 22.60
- S100R (p.Ser100Arg), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, Variant assessed as somatic; moderate impact.
- V101A (p.Val101Ala), Ensembl rs2096281737
Public GCK analysis runs
- GCK analysis run — GCK (1,184 variants) — completed 2026-08-18