GNAS (P63092) variants and mutations
GNAS (also known as P63092) is a human protein-coding gene encoding a guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein. It produces the stimulatory G-alpha subunit that activates adenylyl cyclase downstream of many hormone receptors, with complex tissue-specific imprinting at the locus. Inactivating variants cause pseudohypoparathyroidism-spectrum disorders, while activating somatic variants cause McCune-Albright syndrome and some endocrine tumors. This analysis covers 1,283 GNAS variants and mutations. Of these, 55% have computational variant effect predictions. Disease context includes pseudohypoparathyroidism type 1A, pseudohypoparathyroidism type 1C, and McCune-Albright syndrome. Example GNAS variants include M1A, M1V, and M1I.
Variant analysis overview
- Gene: GNAS
- Protein: P63092
- UniProt accession: P63092
- Organism: Homo sapiens
- Variants analyzed: 1283
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 984 unspecified-consequence records; 175 missense variants; 25 frameshift variants; 76 synonymous variants; 9 stop-gained variants; 10 in-frame deletions; 1 in-frame insertions; 1 stop retained variant; 1 splice-region variants; 1 substitution
- Prediction scores: 707 variants have prediction scores (55% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pseudohypoparathyroidism type 1A, pseudohypoparathyroidism type 1C, McCune-Albright syndrome, Albright hereditary osteodystrophy, pseudohypoparathyroidism type 1B, ACTH-independent macronodular adrenal hyperplasia 1, progressive osseous heteroplasia, pseudopseudohypoparathyroidism, pituitary adenoma 3, multiple types, pseudohypoparathyroidism, gnas-related disorder, hereditary disease.
Protein structure and variant hotspots
- Protein features: 1 domains; 7 binding sites; 2 post-translational modification sites.
- Structural context: 1,157 variants have structural context.
- PTM context: 10 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 GNAS variants
Examples include M1A, M1V, M1I, M1L, M1T, M1R, G2V, C3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1A (p.Met1Ala), rs2516794817, ClinGen CA2580098305, ClinVar RCV002847558, Pathogenic, not provided
- M1V (p.Met1Val), rs137854530, ClinGen CA126055, ClinVar RCV000017278, ClinVar RCV000522303, MetaLR 0.87, MetaSVM 0.94, Uncertain significance, Progressive osseous heteroplasia; McCune-Albright syndrome; Pseudohypoparathyroi
- M1I (p.Met1Ile), rs2145914268, ClinGen CA409448617, ClinVar RCV001806426, MetaLR 0.85, MetaSVM 0.72, Pathogenic, not provided
- M1L (p.Met1Leu), rs137854530, ClinGen CA16620942, ClinVar RCV000483377, MetaLR 0.87, MetaSVM 0.94, Pathogenic, not provided
- M1T (p.Met1Thr), rs1555883949, ClinGen CA409448615, ClinVar RCV000595919, ClinVar RCV002222189, MetaLR 0.88, MetaSVM 0.87, Pathogenic, See cases; Autosomal dominant GNAS-related disorders; not provided
- M1R (p.Met1Arg), rs760203169, gnomAD 20-58840878-T-G, CADD 20.50, SIFT 0.07
- G2V (p.Gly2Val), rs2516795072, ClinGen CA409448625, ClinVar RCV002842048, REVEL 0.54, CADD 18.10, Uncertain significance, not provided
- C3S (p.Cys3Ser), rs1064794045, ClinGen CA16620943, ClinVar RCV000484773, Ensembl rs1064794045, REVEL 0.72, CADD 19.20, Pathogenic, not provided
- C3Y (p.Cys3Tyr), NCI-TCGA Cosmic COSV9966, cosmic curated COSV99668, REVEL 0.76, CADD 19.50, Variant assessed as somatic; moderate impact.
- C3F (p.Cys3Phe), gnomAD 20-58840168-G-T, CADD 26.30, SIFT 0.00
- C3C (p.Cys3Cys), rs772759887, gnomAD 20-58840169-C-T, CADD 18.10
- L4H (p.Leu4His), gnomAD rs1233534637, REVEL 0.56, CADD 19.80
- L4L (p.Leu4Leu), rs778743536, gnomAD 20-58840867-C-T, CADD 19.70
- L4V (p.Leu4Val), rs2085688250, gnomAD 20-58840868-C-G, CADD 19.20, SIFT 0.07
- L4R (p.Leu4Arg), rs745570313, gnomAD 20-58840869-T-G, CADD 20.50, SIFT 0.04
- L4P (p.Leu4Pro), rs745570313, gnomAD 20-58840869-T-C, CADD 20.70, SIFT 0.03
- G5R (p.Gly5Arg), gnomAD rs1349914271, REVEL 0.47, CADD 19.30, Uncertain significance, GNAS-related disorder
- G5V (p.Gly5Val), cosmic curated COSV55672, REVEL 0.58, CADD 19.20
- G5S (p.Gly5Ser), rs1230896240, gnomAD 20-58840179-G-A, CADD 27.40, SIFT 0.00
- G5C (p.Gly5Cys), gnomAD 20-58840179-G-T, CADD 28.70, SIFT 0.00
- G5D (p.Gly5Asp), gnomAD 20-58840180-G-A, CADD 27.10, SIFT 0.00
- G5G (p.Gly5Gly), gnomAD 20-58840181-C-T, CADD 20.00
- N6D (p.Asn6Asp), Ensembl rs2145914545, REVEL 0.34, CADD 20.40
- N6T (p.Asn6Thr), Ensembl rs747930447, REVEL 0.38, CADD 20.50
- S7G (p.Ser7Gly), Ensembl rs2089375186, REVEL 0.28, CADD 19.90
- S7N (p.Ser7Asn), ExAC rs770736594, gnomAD rs770736594, REVEL 0.32, CADD 20.10
- S7F (p.Ser7Phe), rs767657815, gnomAD 20-58840120-C-T, CADD 26.50, SIFT 0.03
- S7S (p.Ser7Ser), gnomAD 20-58840885-A-G, CADD 17.90
- K8* (p.Lys8Ter), rs2145914732, ClinGen CA2573157185, ClinVar RCV001915812, Pathogenic
- T9I (p.Thr9Ile), rs901936182, ClinGen CA316320584, ClinVar RCV003887214, TOPMed rs901936182, REVEL 0.36, CADD 19.90, Uncertain significance, not provided
- T9N (p.Thr9Asn), NCI-TCGA TCGA novel, REVEL 0.22, CADD 19.50, Variant assessed as somatic; moderate impact.
- E10* (p.Glu10Ter), cosmic curated COSV99670, CADD 19.90
- E10K (p.Glu10Lys), 1000Genomes rs200163406, ExAC rs200163406, TOPMed rs200163406, gnomAD rs200163406, REVEL 0.36, CADD 20.40, Uncertain significance, GNAS-related disorder
- E10Q (p.Glu10Gln), cosmic curated COSV55691, 1000Genomes rs200163406, ExAC rs200163406, TOPMed rs200163406, REVEL 0.24, CADD 20.00, Uncertain significance
- E10V (p.Glu10Val), rs1208964733, gnomAD 20-58840848-A-T, CADD 19.80, SIFT 0.02
- D11V (p.Asp11Val), cosmic curated COSV10810, REVEL 0.55, CADD 20.70
- D11Y (p.Asp11Tyr), gnomAD 20-58840110-G-T, CADD 28.30, SIFT 0.00
- D11E (p.Asp11Glu), rs767440362, gnomAD 20-58840111-A-AAT, CADD 28.10
- D11D (p.Asp11Asp), rs2085660791, gnomAD 20-58840112-T-C, CADD 20.50
- D11N (p.Asp11Asn), rs746736450, gnomAD 20-58840161-G-A, CADD 27.90, SIFT 0.00
- D11H (p.Asp11His), gnomAD 20-58840161-G-C, CADD 27.20, SIFT 0.00
- D11G (p.Asp11Gly), gnomAD 20-58840162-A-G, CADD 27.10, SIFT 0.00
- Q12* (p.Gln12Ter), rs797045046, ClinGen CA250351, ClinVar RCV000191090, ClinVar RCV001265981, CADD 18.90, Pathogenic
- Q12E (p.Gln12Glu), gnomAD rs797045046, REVEL 0.24, CADD 18.60, Pathogenic
- Q12P (p.Gln12Pro), rs1225314176, gnomAD 20-58840129-A-C, CADD 22.30, SIFT 0.05
- Q12R (p.Gln12Arg), rs1225314176, gnomAD 20-58840129-A-G, CADD 22.20, SIFT 0.06
- Q12Q (p.Gln12Gln), rs1274269300, gnomAD 20-58840133-G-A, CADD 19.20
- Q12H (p.Gln12His), rs2085688169, gnomAD 20-58840858-CCAGA, CADD 18.40
- R13H (p.Arg13His), ExAC rs767014239, gnomAD rs767014239, REVEL 0.35, CADD 18.30
- R13G (p.Arg13Gly), rs202131370, gnomAD 20-58840113-C-G, CADD 27.50, SIFT 0.00
- R13W (p.Arg13Trp), rs202131370, gnomAD 20-58840113-C-T, CADD 31.00, SIFT 0.00
- R13Q (p.Arg13Gln), rs139302910, gnomAD 20-58840114-G-A, CADD 29.20, SIFT 0.00
- R13L (p.Arg13Leu), gnomAD 20-58840114-G-T, CADD 28.80, SIFT 0.00
- R13P (p.Arg13Pro), rs139302910, gnomAD 20-58840114-G-C, CADD 29.50, SIFT 0.00
- R13R (p.Arg13Arg), gnomAD 20-58840115-G-T, CADD 5.11
- R13M (p.Arg13Met), gnomAD 20-58840117-G-T, CADD 27.80, SIFT 0.00
- R13K (p.Arg13Lys), gnomAD 20-58840117-G-A, CADD 27.00, SIFT 0.00
- R13S (p.Arg13Ser), gnomAD 20-58840137-C-A, CADD 26.80, SIFT 0.00
- R13C (p.Arg13Cys), rs1207504302, gnomAD 20-58840137-C-T, CADD 29.90, SIFT 0.00
- R13* (p.Arg13Ter), rs2085661524, gnomAD 20-58840140-C-T, CADD 36.00
- N14D (p.Asn14Asp), gnomAD rs1417787139, REVEL 0.26, CADD 19.60
- N14S (p.Asn14Ser), rs752140999, ClinGen CA9926874, ClinVar RCV004531806, ClinVar RCV005030358, REVEL 0.15, CADD 19.40, Uncertain significance, Pseudohypoparathyroidism type 1C; Pseudohypoparathyroidism type 1B; Pseudopseudo
- N14I (p.Asn14Ile), gnomAD 20-58840152-AAT-A, CADD 24.50
- N14K (p.Asn14Lys), rs1430025682, gnomAD 20-58840160-C-A, CADD 24.60, SIFT 0.01
- N14N (p.Asn14Asn), gnomAD 20-58840160-C-T, CADD 19.70
- E15* (p.Glu15Ter), cosmic curated COSV55681, CADD 19.50
- E15K (p.Glu15Lys), NCI-TCGA Cosmic COSV5567, cosmic curated COSV55679, NCI-TCGA Cosmic COSV5568, REVEL 0.59, CADD 19.90, Uncertain significance, not provided
- E16D (p.Glu16Asp), cosmic curated COSV55672, CADD 14.70
- E16G (p.Glu16Gly), NCI-TCGA TCGA novel, REVEL 0.38, CADD 21.10, Variant assessed as somatic; moderate impact.
- E16K (p.Glu16Lys), rs2516796853, ClinGen CA409448714, ClinVar RCV003879558, REVEL 0.40, CADD 20.10, Uncertain significance, not provided
- A18C (p.Ala18Cys), gnomAD 20-58840124-G-GT, CADD 27.50
- A18T (p.Ala18Thr), gnomAD 20-58840125-G-A, CADD 23.70, SIFT 0.00
- A18A (p.Ala18Ala), gnomAD 20-58840127-T-C, CADD 21.20
- A18V (p.Ala18Val), rs778940007, gnomAD 20-58840144-C-T, CADD 26.40, SIFT 0.00
- A18D (p.Ala18Asp), gnomAD 20-58840854-C-A, CADD 15.60, SIFT 0.13
- Q19* (p.Gln19Ter), rs2089380075, ClinGen CA409448737, ClinVar RCV001817685, TOPMed rs2089380075, CADD 18.90, Pathogenic
- Q19E (p.Gln19Glu), TOPMed rs2089380075, REVEL 0.33, CADD 18.60, Pathogenic
- R20C (p.Arg20Cys), rs967292772, gnomAD 20-58840182-C-T, CADD 29.50, SIFT 0.00
- R20L (p.Arg20Leu), rs774700482, gnomAD 20-58840183-G-T, CADD 29.50, SIFT 0.00
- R20H (p.Arg20His), rs774700482, gnomAD 20-58840183-G-A, CADD 29.80, SIFT 0.00
- R20R (p.Arg20Arg), gnomAD 20-58840184-C-T, CADD 20.50
- R20G (p.Arg20Gly), rs1211258431, gnomAD 20-58840185-C-G, CADD 27.80, SIFT 0.00
- R20W (p.Arg20Trp), gnomAD 20-58840185-C-T, CADD 31.00, SIFT 0.00
- R20Q (p.Arg20Gln), rs2085663119, gnomAD 20-58840186-G-A, CADD 29.80, SIFT 0.00
- E21K (p.Glu21Lys), TOPMed rs2089380994, REVEL 0.24, CADD 17.50
- A22S (p.Ala22Ser), cosmic curated COSV55683, REVEL 0.32, CADD 19.40
- A22P (p.Ala22Pro), rs759833927, gnomAD 20-58840188-G-C, CADD 25.20, SIFT 0.01
- A22T (p.Ala22Thr), gnomAD 20-58840188-G-A, CADD 23.40, SIFT 0.14
- A22V (p.Ala22Val), gnomAD 20-58840189-C-T, CADD 23.80, SIFT 0.01
- A22G (p.Ala22Gly), rs1346202606, gnomAD 20-58840192-C-G, CADD 24.00, SIFT 0.00
- A22A (p.Ala22Ala), rs1208595553, gnomAD 20-58840193-C-T, CADD 19.90
- K25N (p.Lys25Asn), cosmic curated COSV55687, cosmic curated COSV55681, TOPMed rs1326256762, gnomAD rs1326256762, REVEL 0.23, CADD 18.50, Likely benign
- I26M (p.Ile26Met), NCI-TCGA TCGA novel, REVEL 0.54, CADD 16.40, Variant assessed as somatic; moderate impact.
- I26V (p.Ile26Val), rs2085662717, gnomAD 20-58840176-A-G, CADD 22.40, SIFT 0.01
- I26T (p.Ile26Thr), rs537714939, gnomAD 20-58840177-T-C, CADD 25.40, SIFT 0.00
- I26I (p.Ile26Ile), rs558969394, gnomAD 20-58840223-C-T, CADD 17.60
- E27K (p.Glu27Lys), cosmic curated COSV10454, CADD 17.40
- K28* (p.Lys28Ter), rs2516798313, ClinGen CA409448805, ClinVar RCV004534334, ClinVar RCV006616897, CADD 19.80, Pathogenic
- K28R (p.Lys28Arg), TOPMed rs2089382943, REVEL 0.31, CADD 20.20
- Q29* (p.Gln29Ter), rs1057518907, ClinGen CA16043565, cosmic curated COSV55670, ClinVar RCV000414783, CADD 19.30, Pathogenic
- Q29E (p.Gln29Glu), Ensembl rs1057518907, REVEL 0.40, CADD 18.90, Pathogenic
- L30P (p.Leu30Pro), rs1220130891, gnomAD 20-58840162-A-AC, CADD 27.60
- L30M (p.Leu30Met), rs747725720, gnomAD 20-58840164-C-A, CADD 25.00, SIFT 0.00
- L30L (p.Leu30Leu), rs747725720, gnomAD 20-58840164-C-T, CADD 18.50
- L30Q (p.Leu30Gln), gnomAD 20-58840187-G-GGC, CADD 27.70
- L30I (p.Leu30Ile), gnomAD 20-58840200-C-A, CADD 23.60, SIFT 0.00
- L30F (p.Leu30Phe), gnomAD 20-58840209-C-T, CADD 27.10, SIFT 0.00
- Q31* (p.Gln31Ter), rs2089384365, ClinGen CA409448932, ClinVar RCV001589997, ClinVar RCV002501956, CADD 18.50, Pathogenic
- Q31H (p.Gln31His), rs780295677, ClinGen CA409448939, ClinVar RCV003699155, REVEL 0.51, CADD 19.10, Uncertain significance, not provided
- Q31K (p.Gln31Lys), Ensembl rs2089384365, REVEL 0.33, CADD 18.00, Pathogenic
- K32R (p.Lys32Arg), cosmic curated COSV10500, Ensembl rs2145916069, REVEL 0.33, CADD 19.70
- D33N (p.Asp33Asn), rs1255226034, ClinGen CA409448958, ClinVar RCV003332510, REVEL 0.61, CADD 20.20, Uncertain significance, not provided
- D33Y (p.Asp33Tyr), gnomAD rs1255226034, REVEL 0.71, CADD 19.70
- K34R (p.Lys34Arg), Ensembl rs1944236486, REVEL 0.18, CADD 18.90, Uncertain significance
- K34T (p.Lys34Thr), rs1944236486, ClinGen CA409448978, ClinVar RCV001572222, Ensembl rs1944236486, REVEL 0.58, CADD 18.70, Uncertain significance, not provided
- Q35* (p.Gln35Ter), rs2089386059, ClinGen CA409448990, ClinVar RCV001267237, ClinVar RCV001760312, CADD 19.00, Pathogenic
- Q35H (p.Gln35His), ExAC rs747013992, TOPMed rs747013992, gnomAD rs747013992, REVEL 0.26, CADD 16.90, Likely benign
- V36I (p.Val36Ile), TOPMed rs1160685190, gnomAD rs1160685190, REVEL 0.18, CADD 17.90, Uncertain significance, Inborn genetic diseases; not specified
- V36L (p.Val36Leu), TOPMed rs1160685190, gnomAD rs1160685190, REVEL 0.23, CADD 17.60, Uncertain significance
- V36F (p.Val36Phe), rs78536121, gnomAD 20-58840856-G-T, CADD 12.50, SIFT 0.11
- V36A (p.Val36Ala), rs1205141340, gnomAD 20-58840857-T-C, CADD 14.90, SIFT 0.49
- Y37F (p.Tyr37Phe), ExAC rs777619747, REVEL 0.29, CADD 19.10
- Y37* (p.Tyr37Ter), rs2145469835, gnomAD 20-58840157-C-A, CADD 36.00
- R38G (p.Arg38Gly), TOPMed rs994421324, gnomAD rs994421324, REVEL 0.31, CADD 16.20, Likely benign
- R38W (p.Arg38Trp), TOPMed rs994421324, gnomAD rs994421324, REVEL 0.41, CADD 16.40, Uncertain significance, Pseudopseudohypoparathyroidism; Pituitary adenoma 3, multiple types; ACTH-indepe
- A39D (p.Ala39Asp), Ensembl rs2145916621, REVEL 0.29, CADD 17.60
- A39T (p.Ala39Thr), gnomAD 20-58840197-G-A, CADD 28.70, SIFT 0.00
- A39S (p.Ala39Ser), gnomAD 20-58840197-G-T, CADD 27.10, SIFT 0.00
- A39G (p.Ala39Gly), rs1449469660, gnomAD 20-58840198-C-G, CADD 26.80, SIFT 0.00
- A39A (p.Ala39Ala), rs1190126697, gnomAD 20-58840199-G-A, CADD 16.20
- T40P (p.Thr40Pro), Ensembl rs2145916699, MetaLR 0.66, MetaSVM 0.00
- T40T (p.Thr40Thr), rs767745741, gnomAD 20-58840196-C-T, CADD 17.30
- T40A (p.Thr40Ala), gnomAD 20-58840245-A-G, CADD 17.70, SIFT 0.19
- T40N (p.Thr40Asn), gnomAD 20-58840246-C-A, CADD 24.80, SIFT 0.01
- T40I (p.Thr40Ile), gnomAD 20-58840246-C-T, CADD 25.70, SIFT 0.00
- H41P (p.His41Pro), Ensembl rs2145916816, MetaLR 0.76, MetaSVM 0.39
- H41Y (p.His41Tyr), rs2516800364, ClinGen CA409449043, ClinVar RCV003031619, REVEL 0.34, CADD 19.70, Uncertain significance, not provided
- H41R (p.His41Arg), rs1389217949, gnomAD 20-58840150-A-G, CADD 25.80, SIFT 0.01
- R42C (p.Arg42Cys), rs2145916888, ClinGen CA409449059, ClinVar RCV003050558, ClinVar RCV004536549, REVEL 0.73, CADD 17.90, Pathogenic, GNAS-related disorder; not provided; Inborn genetic diseases
- R42H (p.Arg42His), rs1057520715, ClinGen CA16608477, ClinVar RCV000429080, Ensembl rs1057520715, REVEL 0.57, CADD 20.20, Likely pathogenic, not provided
- R42S (p.Arg42Ser), rs2145916888, ClinGen CA409449055, ClinVar RCV001732160, Ensembl rs2145916888, REVEL 0.77, CADD 17.50, Pathogenic, Pseudohypoparathyroidism type I A
- R42G (p.Arg42Gly), rs1273364707, gnomAD 20-58840233-C-G, CADD 28.10, SIFT 0.00
- R42L (p.Arg42Leu), rs754780507, gnomAD 20-58840234-G-T, CADD 31.00, SIFT 0.00
- R42R (p.Arg42Arg), rs747808766, gnomAD 20-58840235-C-T, CADD 20.60
- L43M (p.Leu43Met), Ensembl rs2145916985, CADD 23.40, Pathogenic
- L43V (p.Leu43Val), rs2145916985, ClinGen CA409449063, ClinVar RCV001732161, Ensembl rs2145916985, REVEL 0.51, CADD 16.30, Pathogenic, Pseudohypoparathyroidism type I A
- p.Leu41 Ala50del, rs1360636166, gnomAD 20-58840222-TCGCG, CADD 21.30
- L43F (p.Leu43Phe), gnomAD 20-58840227-C-T, CADD 26.70, SIFT 0.00
- L43L (p.Leu43Leu), rs758474465, gnomAD 20-58840229-C-A, CADD 18.40
- L43I (p.Leu43Ile), rs112532266, gnomAD 20-58840230-C-A, CADD 26.10, SIFT 0.00
- L45V (p.Leu45Val), gnomAD 20-58840239-C-G, CADD 25.40, SIFT 0.00
- L45F (p.Leu45Phe), rs777218004, gnomAD 20-58840239-C-T, CADD 26.80, SIFT 0.00
- L45P (p.Leu45Pro), gnomAD 20-58840240-T-C, CADD 25.10, SIFT 0.00
- L46R (p.Leu46Arg), rs1600976255, ClinGen CA409449096, ClinVar RCV000850178, ClinVar RCV005054277, AlphaMissense 1.00, MetaLR 0.93, Conflicting interpretations, Pseudohypoparathyroidism type 1C; Pseudohypoparathyroidism type 1B; Pseudopseudo
- G47D (p.Gly47Asp), rs2516902294, ClinGen CA409449536, ClinVar RCV003886327, Likely pathogenic, See cases
- G47S (p.Gly47Ser), rs2516801467, cosmic curated COSV10881, ClinGen CA409449099, ClinVar RCV004536906, REVEL 0.86, CADD 20.70, Likely pathogenic, GNAS-related disorder
- A48S (p.Ala48Ser), gnomAD 20-58840236-G-T, CADD 27.40, SIFT 0.00
- A48T (p.Ala48Thr), gnomAD 20-58840236-G-A, CADD 29.20, SIFT 0.00
- A48Q (p.Ala48Gln), gnomAD 20-58840237-CCCTT, CADD 32.00
- A48V (p.Ala48Val), rs755781835, gnomAD 20-58840237-C-T, CADD 27.50, SIFT 0.00
- A48A (p.Ala48Ala), gnomAD 20-58840238-C-T, CADD 20.50
- A48P (p.Ala48Pro), rs557714686, gnomAD 20-58840242-G-C, CADD 29.20, SIFT 0.00
- A48D (p.Ala48Asp), gnomAD 20-58840255-C-A, CADD 25.60, SIFT 0.00
- p.Ala56 Arg61del, gnomAD 20-58840265-GCAGC, CADD 21.30
- A48E (p.Ala48Glu), rs141238454, gnomAD 20-58840273-C-A, CADD 26.40, SIFT 0.02
- G49A (p.Gly49Ala), cosmic curated COSV55688
- G49V (p.Gly49Val), cosmic curated COSV55674, MetaLR 0.74, MetaSVM 0.83
- E50Q (p.Glu50Gln), cosmic curated COSV55674, MetaLR 0.72, MetaSVM 0.74
- S51C (p.Ser51Cys), rs2516902410, ClinGen CA409449582, ClinVar RCV004395442, Uncertain significance, Inborn genetic diseases
- S51F (p.Ser51Phe), NCI-TCGA Cosmic COSV5567, cosmic curated COSV55679, Variant assessed as somatic; moderate impact.
- S51L (p.Ser51Leu), gnomAD 20-58840208-GCT-G, CADD 32.00
- S51S (p.Ser51Ser), rs764128447, gnomAD 20-58840214-C-T, CADD 19.70
- G52C (p.Gly52Cys), Ensembl rs2146005656, Likely pathogenic
- G52R (p.Gly52Arg), rs2146005656, ClinGen CA409449586, ClinVar RCV002938937, AlphaMissense 1.00, MetaLR 0.74, Uncertain significance, not provided
- G52S (p.Gly52Ser), rs2146005656, ClinGen CA409449584, ClinVar RCV002226845, Ensembl rs2146005656, AlphaMissense 1.00, MetaLR 0.74, Likely pathogenic, Pseudohypoparathyroidism type I A
- K53E (p.Lys53Glu), rs2146005743, ClinGen CA409449596, ClinVar RCV001994567, NCI-TCGA TCGA novel, AlphaMissense 1.00, MetaLR 0.97, Pathogenic, not provided
- K53T (p.Lys53Thr), cosmic curated COSV10962, MetaLR 0.65, MetaSVM 0.62
- S54G (p.Ser54Gly), gnomAD rs2089973541, REVEL 0.92, CADD 29.90
- S54R (p.Ser54Arg), cosmic curated COSV10501, REVEL 0.86, CADD 27.70
- T55A (p.Thr55Ala), rs797044895, ClinGen CA204715, cosmic curated COSV55670, ClinVar RCV000190719, AlphaMissense 1.00, MetaLR 0.94, Likely pathogenic, Inborn genetic diseases
Public GNAS analysis runs
- GNAS analysis run — GNAS (1,283 variants) — completed 2026-08-20