NRAS (GTPase NRas) variants and mutations
NRAS (also known as GTPase NRas) is a human protein-coding gene encoding a GTPase protein. Its active GTP-bound state drives RAF-MEK-ERK and PI3K signaling downstream of growth-factor receptors. Somatic activating variants are common drivers of melanoma, leukemia, and other cancers, while germline activating variants can cause Noonan syndrome. This analysis covers 800 NRAS variants and mutations. Of these, 60% have computational variant effect predictions. Disease context includes Noonan syndrome, Noonan syndrome 6, and large congenital melanocytic nevus. Example NRAS variants include p.Met1dup, T2A, and T2I.
Variant analysis overview
- Gene: NRAS
- Protein: GTPase NRas
- UniProt accession: P01111
- Organism: Homo sapiens
- Variants analyzed: 800
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 663 unspecified-consequence records; 81 synonymous variants; 9 frameshift variants; 40 missense variants; 2 in-frame insertions; 2 in-frame deletions; 2 splice-region variants; 1 substitution
- Prediction scores: 477 variants have prediction scores (60% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Noonan syndrome, Noonan syndrome 6, large congenital melanocytic nevus, nevus, epidermal, acute myeloid leukemia, autoimmune lymphoproliferative syndrome type 4, melanoma, cancer, juvenile myelomonocytic leukemia, plasma cell myeloma, RAS-associated autoimmune leukoproliferative disease, nevus.
Protein structure and variant hotspots
- Protein features: 4 binding sites; 2 post-translational modification sites.
- 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, ClinGen, MaveDB, LitVar.
Notable NRAS variants
Examples include p.Met1dup, T2A, T2I, T2S, T2N, E3*, E3A, E3D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- p.Met1dup, rs755334563, gnomAD 1-114716156-G-GTC, CADD 22.70
- T2A (p.Thr2Ala), rs1310992906, ClinGen CA341742845, ClinVar RCV003038929, gnomAD rs1310992906, AlphaMissense 0.30, MetaLR 0.08, Uncertain significance, RASopathy
- T2I (p.Thr2Ile), rs1659160002, ClinGen CA341742841, ClinVar RCV001290573, Ensembl rs1659160002, AlphaMissense 0.78, MetaLR 0.20, Uncertain significance, not specified
- T2S (p.Thr2Ser), Ensembl rs1659160002, REVEL 0.27, AlphaMissense 0.30, Uncertain significance
- T2N (p.Thr2Asn), gnomAD 1-114716156-G-T, REVEL 0.26, CADD 24.60
- E3* (p.Glu3Ter), Ensembl rs2101744366
- E3A (p.Glu3Ala), NCI-TCGA Cosmic COSV9979, Variant assessed as somatic; moderate impact.
- E3D (p.Glu3Asp), 1000Genomes rs559229605, ExAC rs559229605, gnomAD rs559229605
- E3G (p.Glu3Gly), Ensembl rs2101744362
- E3Q (p.Glu3Gln), Ensembl rs2101744366
- E3V (p.Glu3Val), Ensembl rs2101744362, SIFT 0.00
- E3E (p.Glu3Glu), rs559229605, gnomAD 1-114716152-C-T, CADD 14.10
- Y4* (p.Tyr4Ter), Ensembl rs2101744350, CADD 36.00
- Y4C (p.Tyr4Cys), Ensembl rs2101744352
- Y4F (p.Tyr4Phe), Ensembl rs2101744352
- Y4S (p.Tyr4Ser), Ensembl rs2101744352, SIFT 0.00
- K5* (p.Lys5Ter), Ensembl rs2101744345
- K5N (p.Lys5Asn), Ensembl rs2101744343, REVEL 0.76, CADD 28.50
- L6P (p.Leu6Pro), Ensembl rs2101744337
- L6V (p.Leu6Val), Ensembl rs2101744339
- L6R (p.Leu6Arg), gnomAD 1-114716142-CCA-C, CADD 32.00
- L6L (p.Leu6Leu), rs2101744332, gnomAD 1-114716143-C-T, CADD 15.00
- V7A (p.Val7Ala), TOPMed rs1659159794, gnomAD rs1659159794, REVEL 0.78, CADD 30.00
- V7E (p.Val7Glu), TOPMed rs1659159794, gnomAD rs1659159794
- V7G (p.Val7Gly), TOPMed rs1659159794, gnomAD rs1659159794
- V7L (p.Val7Leu), Ensembl rs2101744327
- V7M (p.Val7Met), Ensembl rs2101744327
- V8A (p.Val8Ala), Ensembl rs2101744309
- V8L (p.Val8Leu), Ensembl rs2101744314, Uncertain significance
- V8M (p.Val8Met), rs2101744314, ClinGen CA341742748, ClinVar RCV001891891, Ensembl rs2101744314, AlphaMissense 0.96, MetaLR 0.46, Uncertain significance, RASopathy
- V8V (p.Val8Val), gnomAD 1-114716137-C-T, CADD 14.70
- V9A (p.Val9Ala), Ensembl rs2101744297
- V9F (p.Val9Phe), Ensembl rs1553244682, Uncertain significance
- V9G (p.Val9Gly), Ensembl rs2101744297
- V9I (p.Val9Ile), rs1553244682, ClinGen CA341742733, ClinVar RCV000545519, ClinVar RCV002476203, REVEL 0.47, CADD 26.50, Uncertain significance, Neurocutaneous melanocytosis; Autoimmune lymphoproliferative syndrome type 4; Ep
- V9L (p.Val9Leu), Ensembl rs1553244682, Uncertain significance
- V9del (p.Val9del), rs751917429, gnomAD 1-114716134-AACC-, CADD 22.10
- V9V (p.Val9Val), rs1557983616, gnomAD 1-114716134-A-C, CADD 15.20
- G10* (p.Gly10Ter), Ensembl rs2101744289
- G10A (p.Gly10Ala), Ensembl rs2101744285
- G10E (p.Gly10Glu), Ensembl rs2101744285
- G10R (p.Gly10Arg), Ensembl rs2101744289
- G10V (p.Gly10Val), NCI-TCGA Cosmic COSV5473, Ensembl rs2101744285, SIFT 0.00, Variant assessed as somatic; moderate impact.
- A11E (p.Ala11Glu), Ensembl rs2101744270
- A11G (p.Ala11Gly), Ensembl rs2101744270, Uncertain significance, RASopathy
- A11P (p.Ala11Pro), gnomAD rs1367788342, Likely benign
- A11T (p.Ala11Thr), rs1367788342, ClinGen CA341742696, NCI-TCGA Cosmic COSV5473, ClinVar RCV000680636, REVEL 0.41, CADD 23.40, Uncertain significance, RASopathy
- A11V (p.Ala11Val), Ensembl rs2101744270, SIFT 0.01
- G12A (p.Gly12Ala), rs121913237, ClinGen CA280928, NCI-TCGA Cosmic COSV5473, REVEL 0.69, CADD 26.10, Pathogenic/Likely pathogenic, Noonan syndrome and Noonan-related syndrome; RASopathy; Colorectal cancer
- G12C (p.Gly12Cys), rs121913250, ClinGen CA297020, NCI-TCGA Cosmic COSV5473, AlphaMissense 1.00, MetaLR 0.58, Pathogenic, not provided
- G12D (p.Gly12Asp), rs121913237, Civic 878, ClinGen CA130425, NCI-TCGA Cosmic COSV5473, REVEL 0.78, CADD 24.70, Pathogenic/Likely pathogenic, NRAS-related disorder; Noonan syndrome and Noonan-related syndrome; Cardiovascul
- G12E (p.Gly12Glu), Ensembl rs2101744245
- G12F (p.Gly12Phe), rs2101744255, ClinGen CA2580617805, ClinVar RCV003896707, Likely pathogenic, NRAS-related disorder
- G12R (p.Gly12Arg), rs121913250, ClinGen CA297030, NCI-TCGA Cosmic COSV5473, AlphaMissense 1.00, MetaLR 0.58, Pathogenic, not provided; Noonan syndrome 6; Increased nuchal translucency
- G12S (p.Gly12Ser), rs121913250, ClinGen CA180753, NCI-TCGA Cosmic COSV5473, REVEL 0.61, AlphaMissense 1.00, Pathogenic, RASopathy
- G12V (p.Gly12Val), rs121913237, ClinGen CA261525, NCI-TCGA Cosmic COSV5473, REVEL 0.79, CADD 26.50, Pathogenic/Likely pathogenic, Colorectal cancer; not provided; RASopathy
- G12G (p.Gly12Gly), rs759764705, gnomAD 1-114716125-A-C, CADD 16.30
- G13A (p.Gly13Ala), ExAC rs121434596, gnomAD rs121434596, Pathogenic, in CMNS and colorectal cancer
- G13C (p.Gly13Cys), rs121434595, NCI-TCGA Cosmic COSV5473, REVEL 0.77, AlphaMissense 1.00, Pathogenic, in CMNS and colorectal cancer
- G13D (p.Gly13Asp), rs121434596, ClinGen CA123620, NCI-TCGA Cosmic COSV5473, REVEL 0.70, CADD 24.50, Pathogenic/Likely pathogenic, NRAS-related disorder; Acute megakaryoblastic leukemia in down syndrome; not pro
- G13R (p.Gly13Arg), rs121434595, Civic 896, ClinGen CA151261, NCI-TCGA Cosmic COSV5473, REVEL 0.76, AlphaMissense 1.00, Likely pathogenic, not provided; Linear nevus sebaceous syndrome; Noonan syndrome 6
- G13S (p.Gly13Ser), rs121434595, NCI-TCGA Cosmic COSV5473, AlphaMissense 1.00, MetaLR 0.56, Pathogenic, in CMNS and colorectal cancer
- G13V (p.Gly13Val), Ensembl rs2101744219, REVEL 0.79, CADD 27.60, Likely pathogenic, Cardiovascular phenotype; Noonan syndrome 6
- V14G (p.Val14Gly), rs1308441238, ClinGen CA341742653, ClinVar RCV002619475, gnomAD rs1308441238, REVEL 0.91, CADD 32.00, Uncertain significance, RASopathy
- V14I (p.Val14Ile), Ensembl rs2101744200, REVEL 0.70, CADD 26.40
- V14L (p.Val14Leu), Ensembl rs2101744200
- V14V (p.Val14Val), rs1433972399, gnomAD 1-114716119-A-G, CADD 13.60
- G15A (p.Gly15Ala), Ensembl rs2101744191, Uncertain significance, not provided
- G15E (p.Gly15Glu), Ensembl rs2101744191
- G15R (p.Gly15Arg), Ensembl rs2101744194
- G15V (p.Gly15Val), Ensembl rs2101744191, Oncogenic, Acute myeloid leukemia
- G15W (p.Gly15Trp), Ensembl rs2101744194
- G15G (p.Gly15Gly), rs769226183, gnomAD 1-114716116-C-G, CADD 14.30
- K16N (p.Lys16Asn), Ensembl rs2101744184, NCI-TCGA Cosmic COSV5474, SIFT 0.02, Variant assessed as somatic; moderate impact.
- S17C (p.Ser17Cys), Ensembl rs2101744181
- S17G (p.Ser17Gly), Ensembl rs2101744181
- S17N (p.Ser17Asn), Ensembl rs2101744175
- S17R (p.Ser17Arg), Ensembl rs2101744171, Likely benign
- S17T (p.Ser17Thr), Ensembl rs2101744175, SIFT 0.04
- A18G (p.Ala18Gly), Ensembl rs2101744167
- A18P (p.Ala18Pro), 1000Genomes rs121913248, REVEL 0.83, CADD 29.30
- A18S (p.Ala18Ser), 1000Genomes rs121913248
- A18T (p.Ala18Thr), 1000Genomes rs121913248
- A18V (p.Ala18Val), Ensembl rs2101744167, SIFT 0.00
- L19M (p.Leu19Met), gnomAD rs1659158278
- L19Q (p.Leu19Gln), Ensembl rs2101744156, SIFT 0.00
- L19V (p.Leu19Val), gnomAD rs1659158278, REVEL 0.65, CADD 24.00
- L19L (p.Leu19Leu), rs1659158278, gnomAD 1-114716106-G-A, CADD 13.00
- T20A (p.Thr20Ala), Ensembl rs2101744151, Uncertain significance, RASopathy
- T20I (p.Thr20Ile), Ensembl rs2101744149
- T20P (p.Thr20Pro), Ensembl rs2101744151
- T20R (p.Thr20Arg), Ensembl rs2101744149
- T20S (p.Thr20Ser), Ensembl rs2101744151, SIFT 0.00
- T20T (p.Thr20Thr), gnomAD 1-114716101-T-A, CADD 12.20
- I21L (p.Ile21Leu), Ensembl rs2101744144
- I21M (p.Ile21Met), Ensembl rs2101744135
- I21N (p.Ile21Asn), Ensembl rs2101744138
- I21T (p.Ile21Thr), Ensembl rs2101744138, SIFT 0.01
- I21V (p.Ile21Val), Ensembl rs2101744144, REVEL 0.32, CADD 24.30
- Q22* (p.Gln22Ter), rs1178238823, ClinGen CA341742482, ClinVar RCV001763293, ClinVar RCV006616536, CADD 39.00, Uncertain significance
- Q22E (p.Gln22Glu), gnomAD rs1178238823, Uncertain significance
- Q22H (p.Gln22His), Ensembl rs868515153, Oncogenic, Acute myeloid leukemia
- Q22K (p.Gln22Lys), NCI-TCGA Cosmic COSV5473, gnomAD rs1178238823, Uncertain significance
- Q22L (p.Gln22Leu), Ensembl rs1570877514, SIFT 0.00, Uncertain significance
- Q22R (p.Gln22Arg), rs1570877514, ClinGen CA341742477, ClinVar RCV000815786, ClinVar RCV004777892, REVEL 0.66, CADD 28.30, Uncertain significance, not provided; RASopathy
- L23Q (p.Leu23Gln), Ensembl rs2101744113
- L23V (p.Leu23Val), Ensembl rs2101744116
- L23L (p.Leu23Leu), rs771113899, gnomAD 1-114716092-T-C, CADD 14.50
- I24L (p.Ile24Leu), Ensembl rs2101744104
- I24M (p.Ile24Met), TOPMed rs1659157907
- I24N (p.Ile24Asn), rs869025573, ClinGen CA356968, ClinVar RCV000208553, ClinVar RCV000522652, AlphaMissense 0.99, MetaLR 0.61, Likely pathogenic, RASopathy
- Q25* (p.Gln25Ter), Ensembl rs2101744097
- Q25E (p.Gln25Glu), Ensembl rs2101744097
- Q25H (p.Gln25His), 1000Genomes rs570328042, ExAC rs570328042, gnomAD rs570328042
- Q25R (p.Gln25Arg), rs2101744093, ClinGen CA341742396, ClinVar RCV001592708, Ensembl rs2101744093, REVEL 0.68, CADD 27.60, Uncertain significance, not provided
- Q25Q (p.Gln25Gln), rs570328042, gnomAD 1-114716086-C-T, CADD 14.30
- N26K (p.Asn26Lys), Ensembl rs2101744084
- N26S (p.Asn26Ser), ExAC rs773404559, gnomAD rs773404559, REVEL 0.19, CADD 22.50
- N26T (p.Asn26Thr), ExAC rs773404559, gnomAD rs773404559, SIFT 0.00
- H27D (p.His27Asp), Ensembl rs1659157713
- H27N (p.His27Asn), Ensembl rs1659157713
- H27Q (p.His27Gln), Ensembl rs2101744079
- H27Y (p.His27Tyr), Ensembl rs1659157713
- H27H (p.His27His), rs2101744079, gnomAD 1-114716080-G-A, CADD 12.40
- F28I (p.Phe28Ile), Ensembl rs2101744072
- F28L (p.Phe28Leu), Ensembl rs2101744072, Likely benign
- F28V (p.Phe28Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F28Y (p.Phe28Tyr), Ensembl rs2101744070, SIFT 0.10, Uncertain significance, RASopathy
- F28F (p.Phe28Phe), rs1328445116, gnomAD 1-114716077-A-G, CADD 15.30
- V29A (p.Val29Ala), Ensembl rs2101744060
- V29E (p.Val29Glu), Ensembl rs2101744060
- V29I (p.Val29Ile), rs772665803, ClinGen CA1020781, ClinVar RCV001171586, ClinVar RCV005093723, REVEL 0.34, CADD 22.80, Uncertain significance, RASopathy; not provided
- V29V (p.Val29Val), rs748537067, gnomAD 1-114716074-T-C, CADD 12.50
- D30E (p.Asp30Glu), Ensembl rs2101744055
- D30G (p.Asp30Gly), Ensembl rs2101744057
- D30H (p.Asp30His), Ensembl rs2101744058
- D30N (p.Asp30Asn), Ensembl rs2101744058, SIFT 0.70, Uncertain significance, not specified
- E31K (p.Glu31Lys), Ensembl rs2101744051
- E31Q (p.Glu31Gln), Ensembl rs2101744051, SIFT 0.03
- E31E (p.Glu31Glu), rs1274842204, gnomAD 1-114716068-T-C, CADD 13.80
- Y32* (p.Tyr32Ter), NCI-TCGA Cosmic COSV5475, TOPMed rs1466940118, gnomAD rs1466940118, Variant assessed as somatic; high impact.
- Y32C (p.Tyr32Cys), Ensembl rs2101744044
- Y32F (p.Tyr32Phe), Ensembl rs2101744044
- Y32H (p.Tyr32His), Ensembl rs2101744047
- Y32N (p.Tyr32Asn), Ensembl rs2101744047
- Y32Y (p.Tyr32Tyr), rs1466940118, gnomAD 1-114716065-A-G, CADD 14.20
- D33E (p.Asp33Glu), Ensembl rs2101744031, REVEL 0.61, CADD 24.60
- D33G (p.Asp33Gly), Ensembl rs2101744032
- D33H (p.Asp33His), NCI-TCGA Cosmic COSV5475, Ensembl rs2101744037, Variant assessed as somatic; moderate impact.
- D33N (p.Asp33Asn), Ensembl rs2101744037
- D33V (p.Asp33Val), Ensembl rs2101744032, SIFT 0.06
- P34A (p.Pro34Ala), Ensembl rs2101744026
- P34H (p.Pro34His), Ensembl rs397514553, Pathogenic, in KNEN
- P34L (p.Pro34Leu), rs397514553, ClinGen CA130423, NCI-TCGA Cosmic COSV5473, NCI-TCGA Cosmic COSV5475, AlphaMissense 1.00, MetaLR 0.68, Pathogenic, Epidermal nevus
- P34R (p.Pro34Arg), rs397514553, ClinGen CA341742160, ClinVar RCV000994077, Ensembl rs397514553, AlphaMissense 1.00, MetaLR 0.68, Uncertain significance, not provided
- P34S (p.Pro34Ser), Ensembl rs2101744026, SIFT 0.01
- P34T (p.Pro34Thr), Ensembl rs2101744026, REVEL 0.80, CADD 31.00
- P34P (p.Pro34Pro), rs1210648980, gnomAD 1-114716059-G-C, CADD 14.70
- T35I (p.Thr35Ile), gnomAD rs1482529842, REVEL 0.88, CADD 29.90
- T35N (p.Thr35Asn), gnomAD rs1482529842, REVEL 0.80, CADD 29.40
- T35S (p.Thr35Ser), gnomAD rs1482529842, SIFT 0.01, Oncogenic, Acute myeloid leukemia
- T35T (p.Thr35Thr), rs2101743998, gnomAD 1-114716056-G-T, CADD 14.20
- T35A (p.Thr35Ala), gnomAD 1-114716058-T-C, REVEL 0.94, CADD 30.00
- I36K (p.Ile36Lys), Ensembl rs2101743995
- I36M (p.Ile36Met), rs2101743991, ClinGen CA341742123, ClinVar RCV001822085, Ensembl rs2101743991, AlphaMissense 0.99, MetaLR 0.71, Likely pathogenic, Noonan syndrome 6
- I36T (p.Ile36Thr), rs2101743995, ClinGen CA341742127, ClinVar RCV002417527, ClinVar RCV003101066, AlphaMissense 1.00, MetaLR 0.78, Uncertain significance, Cardiovascular phenotype; RASopathy
- E37K (p.Glu37Lys), Ensembl rs2101743987, Oncogenic, Acute myeloid leukemia
- D38A (p.Asp38Ala), Ensembl rs2101742194, REVEL 0.93, CADD 32.00
- D38E (p.Asp38Glu), Ensembl rs2101742190, REVEL 0.69, CADD 24.40
- D38H (p.Asp38His), Ensembl rs2101742200
- D38N (p.Asp38Asn), Ensembl rs2101742200, REVEL 0.59, CADD 33.00
- D38V (p.Asp38Val), Ensembl rs2101742194, SIFT 0.00
- D38Y (p.Asp38Tyr), Ensembl rs2101742200, REVEL 0.89, CADD 34.00
- D38D (p.Asp38Asp), rs2101742190, gnomAD 1-114713976-A-G, CADD 15.10
- D38G (p.Asp38Gly), gnomAD 1-114713977-T-C, REVEL 0.94, CADD 33.00
- S39C (p.Ser39Cys), Ensembl rs139287106, REVEL 0.72, CADD 28.20
- S39F (p.Ser39Phe), Ensembl rs139287106, REVEL 0.73, CADD 28.90
- S39P (p.Ser39Pro), Ensembl rs2101742187
- S39T (p.Ser39Thr), Ensembl rs2101742187
- S39Y (p.Ser39Tyr), Ensembl rs139287106, REVEL 0.80, CADD 27.70
Public NRAS analysis runs
- NRAS analysis run — NRAS (800 variants) — completed 2026-08-18