GNAQ (P50148) variants and mutations
GNAQ (also known as P50148) is a human protein-coding gene encoding a guanine nucleotide-binding protein G(q) subunit alpha protein. It links Gq-coupled receptors to phospholipase C signaling and intracellular calcium release. Somatic activating variants are major drivers of uveal melanoma and Sturge-Weber-associated vascular malformations, depending on the developmental timing and cell type affected. This analysis covers 872 GNAQ variants and mutations. Of these, 44% have computational variant effect predictions. Disease context includes Sturge-Weber syndrome, familial multiple nevi flammei, and congenital hemangioma. Example GNAQ variants include T2I, T2S, and L3R.
Variant analysis overview
- Gene: GNAQ
- Protein: P50148
- UniProt accession: P50148
- Organism: Homo sapiens
- Variants analyzed: 872
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 731 unspecified-consequence records; 76 synonymous variants; 47 missense variants; 4 stop-gained variants; 4 splice-region variants; 8 frameshift variants; 1 in-frame deletions; 1 substitution
- Prediction scores: 380 variants have prediction scores (44% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Sturge-Weber syndrome, familial multiple nevi flammei, congenital hemangioma, uveal melanoma, Abnormality of the skeletal system, capillary malformation, hepatocellular carcinoma, cutaneous melanoma, phakomatosis pigmentovascularis, blue nevus, esophageal adenocarcinoma, hepatobiliary neoplasm.
Protein structure and variant hotspots
- Protein features: 1 domains; 15 binding sites; 2 post-translational modification sites.
- Structural context: 819 variants have structural context.
- PTM context: 7 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 GNAQ variants
Examples include T2I, T2S, L3R, L3V, E4D, I6F, I6L, I6M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- T2I (p.Thr2Ile), ExAC rs780163661, TOPMed rs780163661, gnomAD rs780163661, REVEL 0.39, MetaLR 0.43
- T2S (p.Thr2Ser), ExAC rs780163661, TOPMed rs780163661, gnomAD rs780163661, REVEL 0.33, MetaLR 0.40
- L3R (p.Leu3Arg), gnomAD rs1824054666, REVEL 0.48, MetaLR 0.54
- L3V (p.Leu3Val), gnomAD rs1824054704, REVEL 0.34, MetaLR 0.42
- E4D (p.Glu4Asp), Ensembl rs1059518, REVEL 0.31, MetaLR 0.29
- I6F (p.Ile6Phe), ExAC rs746420387, TOPMed rs746420387, gnomAD rs746420387, REVEL 0.38, MetaLR 0.38
- I6L (p.Ile6Leu), ExAC rs746420387, TOPMed rs746420387, gnomAD rs746420387, REVEL 0.28, MetaLR 0.41
- I6M (p.Ile6Met), ExAC rs779515663, TOPMed rs779515663, gnomAD rs779515663, REVEL 0.31, MetaLR 0.32
- I6T (p.Ile6Thr), TOPMed rs1264916735, REVEL 0.32, MetaLR 0.32
- I6V (p.Ile6Val), ExAC rs746420387, TOPMed rs746420387, gnomAD rs746420387, REVEL 0.24, MetaLR 0.39
- M7L (p.Met7Leu), ExAC rs757711264, TOPMed rs757711264, gnomAD rs757711264, REVEL 0.33, MetaLR 0.49
- A8G (p.Ala8Gly), Ensembl rs1824054288
- A8T (p.Ala8Thr), gnomAD rs1203392784, REVEL 0.46, MetaLR 0.54
- A8V (p.Ala8Val), Ensembl rs1824054288, REVEL 0.39, MetaLR 0.45
- C9Y (p.Cys9Tyr), Ensembl rs2118632499, REVEL 0.75, MetaLR 0.83
- C10Y (p.Cys10Tyr), NCI-TCGA TCGA novel, REVEL 0.76, MetaLR 0.80, Variant assessed as somatic; moderate impact.
- S12N (p.Ser12Asn), Ensembl rs1824054104, REVEL 0.47, MetaLR 0.66
- E13* (p.Glu13Ter), Ensembl rs2118632468, CADD 36.00
- E14A (p.Glu14Ala), Ensembl rs2118632451
- E14G (p.Glu14Gly), Ensembl rs2118632451, REVEL 0.50, MetaLR 0.62
- A15T (p.Ala15Thr), TOPMed rs1824053956, REVEL 0.37, MetaLR 0.58
- A15V (p.Ala15Val), Ensembl rs2118632430, REVEL 0.29, MetaLR 0.53
- E17K (p.Glu17Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A18V (p.Ala18Val), Ensembl rs2118632423, REVEL 0.52, MetaLR 0.70
- R19Q (p.Arg19Gln), Ensembl rs2118632387, REVEL 0.31, MetaLR 0.39
- R20L (p.Arg20Leu), Ensembl rs2118632361, REVEL 0.69, MetaLR 0.73
- R20W (p.Arg20Trp), Ensembl rs2118632370, REVEL 0.66, MetaLR 0.82
- I21T (p.Ile21Thr), Ensembl rs2118632345, REVEL 0.65, MetaLR 0.73
- I21V (p.Ile21Val), Ensembl rs2118632350, REVEL 0.37, MetaLR 0.57
- N22D (p.Asn22Asp), Ensembl rs2118632334, REVEL 0.45, MetaLR 0.61
- D23E (p.Asp23Glu), Ensembl rs1012464653, REVEL 0.23, MetaLR 0.43
- D23N (p.Asp23Asn), Ensembl rs2118632321, REVEL 0.32, MetaLR 0.50
- I25M (p.Ile25Met), NCI-TCGA Cosmic COSV9968, Variant assessed as somatic; moderate impact.
- E26K (p.Glu26Lys), Ensembl rs2118632300, REVEL 0.66, MetaLR 0.68
- R27W (p.Arg27Trp), ExAC rs767021243, gnomAD rs767021243, REVEL 0.68, MetaLR 0.80
- Q28E (p.Gln28Glu), Ensembl rs2118632279
- L29P (p.Leu29Pro), Ensembl rs2118632266, REVEL 0.83, MetaLR 0.83
- L29V (p.Leu29Val), Ensembl rs2118632272
- R30H (p.Arg30His), Ensembl rs2118632251, REVEL 0.57, MetaLR 0.60
- R31G (p.Arg31Gly), Ensembl rs2118632241, REVEL 0.52, MetaLR 0.71
- D32Y (p.Asp32Tyr), Ensembl rs2118632230, REVEL 0.79, MetaLR 0.81
- R34G (p.Arg34Gly), Ensembl rs2118632211
- R34Q (p.Arg34Gln), Ensembl rs1824053452, REVEL 0.36, MetaLR 0.52
- R34W (p.Arg34Trp), Ensembl rs2118632211, REVEL 0.68, MetaLR 0.79
- D35A (p.Asp35Ala), Ensembl rs1824053410
- D35G (p.Asp35Gly), Ensembl rs1824053410, REVEL 0.45, MetaLR 0.70
- D35H (p.Asp35His), Ensembl rs2118632201
- D35N (p.Asp35Asn), NCI-TCGA TCGA novel, Ensembl rs2118632201, Variant assessed as somatic; moderate impact.
- A36T (p.Ala36Thr), Ensembl rs2118632185, REVEL 0.45, MetaLR 0.64
- R37H (p.Arg37His), Ensembl rs2118632175, REVEL 0.53, MetaLR 0.66
- R38Q (p.Arg38Gln), Ensembl rs2118632170, REVEL 0.36, MetaLR 0.39
- E39D (p.Glu39Asp), Ensembl rs2118632158, REVEL 0.51, MetaLR 0.54
- L40H (p.Leu40His), Ensembl rs2118632149, REVEL 0.61, MetaLR 0.69
- L40I (p.Leu40Ile), Ensembl rs2118632151, REVEL 0.26, MetaLR 0.40
- L40P (p.Leu40Pro), Ensembl rs2118632149, REVEL 0.65, MetaLR 0.76
- K41M (p.Lys41Met), Ensembl rs2118632143, REVEL 0.64, MetaLR 0.75
- L42R (p.Leu42Arg), NCI-TCGA Cosmic COSV5410, Variant assessed as somatic; moderate impact.
- L42V (p.Leu42Val), ExAC rs762737987, gnomAD rs762737987
- L43P (p.Leu43Pro), gnomAD rs1466271329, REVEL 0.90, MetaLR 0.94
- L44P (p.Leu44Pro), Ensembl rs2118632108, REVEL 0.64, MetaLR 0.77
- L45R (p.Leu45Arg), Ensembl rs1824053117
- G46R (p.Gly46Arg), Ensembl rs2118632073, REVEL 0.91, MetaLR 0.98
- G46W (p.Gly46Trp), Ensembl rs2118632073, REVEL 0.87, MetaLR 0.98
- T47I (p.Thr47Ile), Ensembl rs2118276792
- G48* (p.Gly48Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G48V (p.Gly48Val), rs2118276763, ClinGen CA373997226, NCI-TCGA Cosmic COSV9968, ClinVar RCV002254468, AlphaMissense 1.00, MetaLR 0.93, Pathogenic/Likely pathogenic, Sturge-Weber syndrome; not provided
- S50W (p.Ser50Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G51V (p.Gly51Val), NCI-TCGA Cosmic COSV5410, REVEL 0.99, MetaLR 0.99, Variant assessed as somatic; moderate impact.
- T54M (p.Thr54Met), Ensembl rs2118276725, REVEL 0.92, MetaLR 0.96
- F55I (p.Phe55Ile), Ensembl rs2118276689
- K57E (p.Lys57Glu), TOPMed rs1829011020
- Q58* (p.Gln58Ter), Ensembl rs2118276634
- M59I (p.Met59Ile), Ensembl rs2118276585
- M59L (p.Met59Leu), ExAC rs773781296, gnomAD rs773781296, REVEL 0.83, MetaLR 0.81
- R60K (p.Arg60Lys), Ensembl rs2118276568
- I62S (p.Ile62Ser), Ensembl rs1829010800
- I62T (p.Ile62Thr), NCI-TCGA Cosmic COSV5410, Variant assessed as somatic; moderate impact.
- H63R (p.His63Arg), NCI-TCGA Cosmic COSV9968, Variant assessed as somatic; moderate impact.
- H63Y (p.His63Tyr), Ensembl rs2118276524
- G64R (p.Gly64Arg), Ensembl rs2118276506
- G64V (p.Gly64Val), NCI-TCGA Cosmic COSV5410, Variant assessed as somatic; moderate impact.
- S65L (p.Ser65Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S65T (p.Ser65Thr), Ensembl rs2118276461
- G66* (p.Gly66Ter), Ensembl rs2118276422
- D69E (p.Asp69Glu), gnomAD rs1256109740, REVEL 0.34, MetaLR 0.34
- D71Y (p.Asp71Tyr), NCI-TCGA Cosmic COSV5412, Variant assessed as somatic; moderate impact.
- K72R (p.Lys72Arg), Ensembl rs1829010465, REVEL 0.28, MetaLR 0.43
- R73G (p.Arg73Gly), Ensembl rs2118276377
- R73K (p.Arg73Lys), Ensembl rs1829010402
- G74D (p.Gly74Asp), Ensembl rs2118276343, REVEL 0.49, MetaLR 0.57
- T76A (p.Thr76Ala), ExAC rs768341234, gnomAD rs768341234, REVEL 0.42, MetaLR 0.52
- K77N (p.Lys77Asn), Ensembl rs2118276295
- K77R (p.Lys77Arg), rs746699009, ClinGen CA5094687, ClinVar RCV002934701, ExAC rs746699009, REVEL 0.28, MetaLR 0.53, Uncertain significance, Inborn genetic diseases
- V79L (p.Val79Leu), TOPMed rs1369065497, gnomAD rs1369065497, REVEL 0.82, MetaLR 0.86
- Y80D (p.Tyr80Asp), Ensembl rs2118276235
- Y80F (p.Tyr80Phe), TOPMed rs1251821572
- Q81* (p.Gln81Ter), Ensembl rs2118276213
- I83V (p.Ile83Val), TOPMed rs1647480962, REVEL 0.41, MetaLR 0.57, Uncertain significance, Inborn genetic diseases
- F84Y (p.Phe84Tyr), TOPMed rs1192458704, gnomAD rs1192458704, REVEL 0.48, MetaLR 0.64
- T85M (p.Thr85Met), rs761634659, NCI-TCGA Cosmic COSV5411, ExAC rs761634659, gnomAD rs761634659, REVEL 0.41, MetaLR 0.52, Variant assessed as somatic; moderate impact.
- T85P (p.Thr85Pro), NCI-TCGA Cosmic COSV9968, Variant assessed as somatic; moderate impact.
- T85R (p.Thr85Arg), ExAC rs761634659, gnomAD rs761634659
- A86T (p.Ala86Thr), Ensembl rs2118276122
- A86V (p.Ala86Val), Ensembl rs2118276109
- M87I (p.Met87Ile), Ensembl rs1829009386, REVEL 0.34, MetaLR 0.44
- M87V (p.Met87Val), ExAC rs778978521, TOPMed rs778978521, gnomAD rs778978521, REVEL 0.46, MetaLR 0.59
- Q88* (p.Gln88Ter), Ensembl rs1191803927
- Q88E (p.Gln88Glu), Ensembl rs1191803927
- A89P (p.Ala89Pro), Ensembl rs2118276042
- A89T (p.Ala89Thr), Ensembl rs2118276042
- A89V (p.Ala89Val), Ensembl rs2118276026
- M90I (p.Met90Ile), Ensembl rs1829009179, REVEL 0.52, MetaLR 0.41
- M90V (p.Met90Val), Ensembl rs1829009245, REVEL 0.67, MetaLR 0.55
- R92T (p.Arg92Thr), Ensembl rs1136722
- A93S (p.Ala93Ser), gnomAD rs1444819549
- A93T (p.Ala93Thr), gnomAD rs1444819549
- A93V (p.Ala93Val), Ensembl rs2118275967
- D95E (p.Asp95Glu), ExAC rs757129673, gnomAD rs757129673
- D95N (p.Asp95Asn), Ensembl rs2118275951
- T96S (p.Thr96Ser), rs753716491, NCI-TCGA Cosmic COSV5410, ExAC rs753716491, gnomAD rs753716491, REVEL 0.30, MetaLR 0.54, Variant assessed as somatic; moderate impact.
- I99M (p.Ile99Met), gnomAD rs1416428102, REVEL 0.83, MetaLR 0.81
- P100L (p.Pro100Leu), ExAC rs766649624, gnomAD rs766649624, REVEL 0.35, MetaLR 0.66
- P100R (p.Pro100Arg), ExAC rs766649624, gnomAD rs766649624, REVEL 0.54, MetaLR 0.70
- P100T (p.Pro100Thr), Ensembl rs2118275807, REVEL 0.53, MetaLR 0.61
- Y101* (p.Tyr101Ter), 1000Genomes rs200106152, ExAC rs200106152, gnomAD rs200106152, CADD 38.00
- Y101N (p.Tyr101Asn), Ensembl rs2118275776
- K102N (p.Lys102Asn), gnomAD rs1468666506, REVEL 0.28, MetaLR 0.56
- Y103C (p.Tyr103Cys), Ensembl rs77227613, REVEL 0.27, MetaLR 0.42
- Y103H (p.Tyr103His), ExAC rs765827868, TOPMed rs765827868, gnomAD rs765827868, REVEL 0.27, MetaLR 0.42
- Y103S (p.Tyr103Ser), Ensembl rs77227613, MetaLR 0.42, MetaSVM -0.40
- E104G (p.Glu104Gly), 1000Genomes rs200658460
- H105D (p.His105Asp), TOPMed rs1438658973, gnomAD rs1438658973, REVEL 0.31, MetaLR 0.25
- H105R (p.His105Arg), TOPMed rs1829007919, gnomAD rs1829007919, REVEL 0.27, MetaLR 0.32
- H105Y (p.His105Tyr), NCI-TCGA TCGA novel, TOPMed rs1438658973, gnomAD rs1438658973, Variant assessed as somatic; moderate impact.
- N106D (p.Asn106Asp), TOPMed rs1829007847, gnomAD rs1829007847, REVEL 0.67, MetaLR 0.74
- N106I (p.Asn106Ile), gnomAD rs1829007782
- N106S (p.Asn106Ser), gnomAD rs1829007782, REVEL 0.47, MetaLR 0.60
- K107Q (p.Lys107Gln), ExAC rs762200216, gnomAD rs762200216, REVEL 0.23, MetaLR 0.45
- A108V (p.Ala108Val), ESP rs377726080, ExAC rs377726080, TOPMed rs377726080, gnomAD rs377726080, REVEL 0.33, MetaLR 0.47
- H109N (p.His109Asn), gnomAD rs1288502233, REVEL 0.39, MetaLR 0.39
- H109Q (p.His109Gln), TOPMed rs1827002659, gnomAD rs1827002659, REVEL 0.30, MetaLR 0.47
- H109R (p.His109Arg), ExAC rs761095319, TOPMed rs761095319, gnomAD rs761095319, REVEL 0.31, MetaLR 0.47
- A110T (p.Ala110Thr), ExAC rs775821091, gnomAD rs775821091, REVEL 0.66, MetaLR 0.84
- V113I (p.Val113Ile), TOPMed rs1430429958, gnomAD rs1430429958, REVEL 0.40, MetaLR 0.29
- R114* (p.Arg114Ter), NCI-TCGA Cosmic COSV5410, NCI-TCGA Cosmic COSV9968, ExAC rs759080789, TOPMed rs759080789, CADD 40.00, Variant assessed as somatic; high impact.
- R114G (p.Arg114Gly), ExAC rs759080789, TOPMed rs759080789, gnomAD rs759080789, REVEL 0.52, MetaLR 0.61
- R114Q (p.Arg114Gln), TOPMed rs1010141343, gnomAD rs1010141343, REVEL 0.34, MetaLR 0.57
- E115K (p.Glu115Lys), gnomAD rs1425322060, REVEL 0.43, MetaLR 0.46
- V116A (p.Val116Ala), NCI-TCGA TCGA novel, REVEL 0.47, MetaLR 0.61, Variant assessed as somatic; moderate impact.
- V116L (p.Val116Leu), Ensembl rs1383379438
- D117G (p.Asp117Gly), ESP rs371301832, ExAC rs371301832, gnomAD rs371301832
- S122C (p.Ser122Cys), TOPMed rs1351194942, gnomAD rs1351194942, REVEL 0.38, MetaLR 0.61
- S122F (p.Ser122Phe), NCI-TCGA Cosmic COSV5410, Variant assessed as somatic; moderate impact.
- S122P (p.Ser122Pro), TOPMed rs1163999044, gnomAD rs1163999044, REVEL 0.32, MetaLR 0.54
- A123G (p.Ala123Gly), Ensembl rs2118510740
- A123V (p.Ala123Val), Ensembl rs2118510740
- N126T (p.Asn126Thr), Ensembl rs1827001896, REVEL 0.33, MetaLR 0.35
- P127S (p.Pro127Ser), gnomAD rs1827001841, REVEL 0.33, MetaLR 0.44
- Y128F (p.Tyr128Phe), Ensembl rs2118510705
- D130G (p.Asp130Gly), Ensembl rs1827001688, REVEL 0.42, MetaLR 0.59, Uncertain significance, Inborn genetic diseases
- D130N (p.Asp130Asn), rs192927818, ClinGen CA5094643, ClinVar RCV000912112, 1000Genomes rs192927818, REVEL 0.36, MetaLR 0.56, Likely benign, not provided
- A131E (p.Ala131Glu), TOPMed rs1362009464
- A131G (p.Ala131Gly), TOPMed rs1362009464, REVEL 0.55, MetaLR 0.74
- A131T (p.Ala131Thr), Ensembl rs2118510684, REVEL 0.71, MetaLR 0.75, Uncertain significance, not provided
- I132V (p.Ile132Val), gnomAD rs1827001585, REVEL 0.47, MetaLR 0.70
- K133R (p.Lys133Arg), TOPMed rs1827001527
- S134I (p.Ser134Ile), ExAC rs748011987, TOPMed rs748011987, gnomAD rs748011987
- S134N (p.Ser134Asn), ExAC rs748011987, TOPMed rs748011987, gnomAD rs748011987, REVEL 0.36, MetaLR 0.54
- L135V (p.Leu135Val), rs1305477251, NCI-TCGA Cosmic COSV5410, TOPMed rs1305477251, gnomAD rs1305477251, REVEL 0.67, MetaLR 0.81, Variant assessed as somatic; moderate impact.
- N137T (p.Asn137Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P139H (p.Pro139His), Ensembl rs1827001332
- G140R (p.Gly140Arg), Ensembl rs2118510611
- Q142* (p.Gln142Ter), Ensembl rs2118510585
- C144R (p.Cys144Arg), gnomAD rs1295375779
- Y145C (p.Tyr145Cys), Ensembl rs1827000289
- Y145H (p.Tyr145His), Ensembl rs1827000358
- D146H (p.Asp146His), NCI-TCGA Cosmic COSV5412, Variant assessed as somatic; moderate impact.
- R147T (p.Arg147Thr), Ensembl rs2118510524
- R148* (p.Arg148Ter), NCI-TCGA Cosmic COSV5412, Ensembl rs2118510514, CADD 37.00, Variant assessed as somatic; high impact.
- R148Q (p.Arg148Gln), Ensembl rs2118510504, REVEL 0.72, MetaLR 0.83
Public GNAQ analysis runs
- GNAQ analysis run — GNAQ (872 variants) — completed 2026-08-19