RAF1 (P04049) variants and mutations
RAF1 (also known as P04049) is a human protein-coding gene encoding a RAF proto-oncogene serine/threonine-protein kinase protein. It relays activated RAS signals to MEK and ERK and also participates in survival and developmental pathways. Germline activating variants cause Noonan syndrome and related RASopathies, while oncogenic activation contributes to selected cancers. This analysis covers 2,086 RAF1 variants and mutations. Of these, 30% have computational variant effect predictions. Disease context includes autoimmune disorder of central nervous system, asthma, and inflammatory bowel disease. Example RAF1 variants include M1V, M1Y, and M1L.
Variant analysis overview
- Gene: RAF1
- Protein: P04049
- UniProt accession: P04049
- Organism: Homo sapiens
- Variants analyzed: 2086
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,914 unspecified-consequence records; 100 missense variants; 45 synonymous variants; 12 frameshift variants; 11 stop-gained variants; 1 in-frame deletions; 1 stop retained variant; 2 substitution
- Prediction scores: 617 variants have prediction scores (30% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: autoimmune disorder of central nervous system, asthma, inflammatory bowel disease, mirror movements 4, mirror movements 2, familial congenital mirror movements, Benign familial chorea, Increased total eosinophil count, isolated agammaglobulinemia, autosomal dominant severe congenital neutropenia, eosinophilic esophagitis, autosomal agammaglobulinemia.
Protein structure and variant hotspots
- Protein features: 2 domains; 10 binding sites; 20 post-translational modification sites.
- Structural context: 1,073 variants have structural context.
- PTM context: 68 variants overlap post-translational modification sites.
- Experimental data: 69 protein positions have experimental scores. Source: binding assays.
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 RAF1 variants
Examples include M1V, M1Y, M1L, M1K, M1I, E2K, E2E, H3D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1V (p.Met1Val), rs2125453796, ClinGen CA351485294, ClinVar RCV002019360, ClinVar RCV004555630, MetaLR 0.55, MetaSVM 0.15, Uncertain significance, RASopathy; Cardiovascular phenotype; LEOPARD syndrome 2
- M1Y (p.Met1Tyr), gnomAD 14-20891738-C-CT, CADD 17.80
- M1L (p.Met1Leu), rs374635539, gnomAD 14-20891741-A-C, REVEL 0.02, MetaLR 0.00
- M1K (p.Met1Lys), rs779182743, gnomAD 14-20891742-T-A, REVEL 0.04, MetaLR 0.01
- M1I (p.Met1Ile), rs1323908501, gnomAD 14-20891743-G-A, REVEL 0.01, MetaLR 0.01
- E2K (p.Glu2Lys), rs747737990, gnomAD 14-20891750-G-A, REVEL 0.01, MetaLR 0.01
- E2E (p.Glu2Glu), rs368925772, gnomAD 14-20891752-G-A, CADD 0.57
- H3D (p.His3Asp), Ensembl rs2125453788
- H3Y (p.His3Tyr), Ensembl rs2125453788
- H3P (p.His3Pro), rs1877563014, gnomAD 14-20891763-A-C, REVEL 0.04, MetaLR 0.03
- H3Q (p.His3Gln), rs371854422, gnomAD 14-20891764-T-A, REVEL 0.01, MetaLR 0.01
- I4L (p.Ile4Leu), ExAC rs747330424, gnomAD rs747330424
- I4T (p.Ile4Thr), rs2059454224, ClinGen CA351485267, cosmic curated COSV99313, ClinVar RCV003846461, AlphaMissense 0.35, MetaLR 0.25, Uncertain significance, RASopathy
- Q5R (p.Gln5Arg), TOPMed rs2059454121
- Q5Q (p.Gln5Gln), rs149500970, gnomAD 14-20891713-A-G, CADD 2.04
- G6R (p.Gly6Arg), rs1575600689, ClinGen CA351485256, ClinVar RCV000814962, ClinVar RCV002397688, AlphaMissense 0.78, MetaLR 0.54, Uncertain significance, not provided
- A7G (p.Ala7Gly), rs200365094, ClinGen CA69577094, ClinVar RCV001957904, ClinVar RCV003320859, AlphaMissense 0.14, MetaLR 0.39, Uncertain significance, Cardiovascular phenotype; RASopathy; not provided
- W8S (p.Trp8Ser), rs780550449, ClinGen CA2259852, ClinVar RCV001236763, ClinVar RCV002451570, AlphaMissense 0.52, MetaLR 0.44, Uncertain significance, RASopathy; Cardiovascular phenotype
- W8L (p.Trp8Leu), gnomAD 14-20891796-G-T, REVEL 0.31, MetaLR 0.56
- W8* (p.Trp8Ter), gnomAD 14-20891796-G-A, CADD 35.00
- W8C (p.Trp8Cys), gnomAD 14-20891797-G-C, REVEL 0.42, MetaLR 0.63
- K9E (p.Lys9Glu), gnomAD 14-20891696-A-G, REVEL 0.04, MetaLR 0.03
- T10M (p.Thr10Met), rs144637992, ClinGen CA2259851, ClinVar RCV000522586, ClinVar RCV001813497, AlphaMissense 0.17, MetaLR 0.30, Uncertain significance, Cardiovascular phenotype; not provided; Noonan syndrome and Noonan-related syndr
- T10I (p.Thr10Ile), gnomAD 14-20891706-C-T, REVEL 0.03, MetaLR 0.03
- T10S (p.Thr10Ser), rs1462890191, gnomAD 14-20891706-C-G, REVEL 0.09, MetaLR 0.01
- I11F (p.Ile11Phe), rs779001930, ClinGen CA351485223, ClinVar RCV000761113, ClinVar RCV001207035, AlphaMissense 0.07, MetaLR 0.18, Uncertain significance, LEOPARD syndrome 2; Noonan syndrome 5; Dilated cardiomyopathy 1NN
- I11V (p.Ile11Val), ExAC rs779001930, gnomAD rs779001930, Uncertain significance
- I11T (p.Ile11Thr), gnomAD 14-20891715-T-C, REVEL 0.08, MetaLR 0.03
- I11M (p.Ile11Met), rs752773252, gnomAD 14-20891716-T-G, REVEL 0.04, MetaLR 0.03
- S12G (p.Ser12Gly), rs2125453642, ClinGen CA351485217, ClinVar RCV001755058, ClinVar RCV001868549, AlphaMissense 0.09, MetaLR 0.32, Uncertain significance, RASopathy; not provided
- S12F (p.Ser12Phe), gnomAD 14-20891709-C-T, REVEL 0.09, MetaLR 0.03
- N13D (p.Asn13Asp), rs1382771046, ClinGen CA351485209, ClinVar RCV002355164, ClinVar RCV003102450, AlphaMissense 0.11, MetaLR 0.25, Uncertain significance, Cardiovascular phenotype; RASopathy
- N13S (p.Asn13Ser), rs2470448464, ClinGen CA351485207, ClinVar RCV003288340, ClinVar RCV006472268, Uncertain significance, Cardiovascular phenotype; RASopathy
- G14D (p.Gly14Asp), rs757333753, ClinGen CA2259848, cosmic curated COSV10586, ClinVar RCV000475263, AlphaMissense 0.40, MetaLR 0.51, Uncertain significance, not provided; RASopathy
- G14V (p.Gly14Val), ExAC rs757333753, TOPMed rs757333753, gnomAD rs757333753, Uncertain significance
- F15H (p.Phe15His), gnomAD 14-20891699-CTG-C, CADD 21.20
- F15F (p.Phe15Phe), gnomAD 14-20891704-C-T, CADD 0.90
- G16R (p.Gly16Arg), rs867802498, gnomAD 14-20891735-G-A, REVEL 0.16, MetaLR 0.07
- F17S (p.Phe17Ser), rs1454494958, NCI-TCGA Cosmic COSV5258, cosmic curated COSV52580, gnomAD rs1454494958, AlphaMissense 0.16, MetaLR 0.25, Variant assessed as somatic; moderate impact.
- K18R (p.Lys18Arg), rs150944421, ClinGen CA2259847, ClinVar RCV001235542, ClinVar RCV002348793, AlphaMissense 0.23, MetaLR 0.29, Conflicting interpretations, RASopathy; Cardiovascular phenotype; not provided
- K18T (p.Lys18Thr), cosmic curated COSV10634, 1000Genomes rs150944421, ESP rs150944421, ExAC rs150944421, Likely benign
- D19H (p.Asp19His), Ensembl rs2125453562, Uncertain significance, RASopathy
- D19Y (p.Asp19Tyr), NCI-TCGA Cosmic COSV5257, cosmic curated COSV52576, Ensembl rs2125453562, Variant assessed as somatic; moderate impact.
- A20G (p.Ala20Gly), TOPMed rs1438827623
- A20S (p.Ala20Ser), Ensembl rs2125453554
- A20V (p.Ala20Val), rs1438827623, NCI-TCGA Cosmic COSV5258, cosmic curated COSV52582, TOPMed rs1438827623, AlphaMissense 0.09, MetaLR 0.26, Variant assessed as somatic; moderate impact.
- V21A (p.Val21Ala), rs1306287046, ClinGen CA351485152, ClinVar RCV001361509, ClinVar RCV002298937, AlphaMissense 0.09, MetaLR 0.23, Uncertain significance, not provided; RASopathy
- V21E (p.Val21Glu), gnomAD rs1306287046, Uncertain significance
- V21M (p.Val21Met), rs752484962, ClinGen CA2259844, ClinVar RCV001257447, ClinVar RCV002252347, AlphaMissense 0.10, MetaLR 0.28, Likely benign, RASopathy; See cases
- V21I (p.Val21Ile), rs751894020, gnomAD 14-20891690-G-A, REVEL 0.05, MetaLR 0.04
- V21F (p.Val21Phe), rs751894020, gnomAD 14-20891690-G-T, REVEL 0.06, MetaLR 0.04
- F22C (p.Phe22Cys), rs2125453485, ClinGen CA351485145, ClinVar RCV001980310, ClinVar RCV002370663, AlphaMissense 0.15, MetaLR 0.49, Uncertain significance, RASopathy; Cardiovascular phenotype
- F22L (p.Phe22Leu), rs397516824, ClinGen CA134746, cosmic curated COSV52584, ClinVar RCV000037696, AlphaMissense 0.53, MetaLR 0.21, Likely benign, RASopathy
- D23E (p.Asp23Glu), gnomAD rs1312493403
- D23G (p.Asp23Gly), rs966682247, ClinGen CA351485140, ClinVar RCV003297323, AlphaMissense 0.23, MetaLR 0.29, Uncertain significance, Cardiovascular phenotype
- D23N (p.Asp23Asn), rs2059451949, ClinGen CA351485142, ClinVar RCV001241834, gnomAD rs2059451949, AlphaMissense 0.10, MetaLR 0.26, Uncertain significance, RASopathy
- D23V (p.Asp23Val), Ensembl rs966682247
- G24D (p.Gly24Asp), Ensembl rs2059451505
- G24S (p.Gly24Ser), rs1019217338, ClinGen CA69576989, ClinVar RCV000681110, ClinVar RCV001342547, AlphaMissense 0.07, MetaLR 0.26, Uncertain significance, Cardiovascular phenotype; RASopathy; not provided
- S25P (p.Ser25Pro), gnomAD 14-20891756-T-C, REVEL 0.09, MetaLR 0.04
- S25S (p.Ser25Ser), rs1335962557, gnomAD 14-20891758-A-T, CADD 0.26
- S26I (p.Ser26Ile), Ensembl rs2125453413
- S26R (p.Ser26Arg), rs886041229, ClinGen CA10602878, ClinVar RCV000263568, Ensembl rs886041229, AlphaMissense 0.41, MetaLR 0.24, Uncertain significance, RASopathy
- C27Y (p.Cys27Tyr), Ensembl rs2125453390
- C27R (p.Cys27Arg), gnomAD 14-20891717-T-C, REVEL 0.04, MetaLR 0.02
- C27* (p.Cys27Ter), gnomAD 14-20891719-T-A, CADD 26.60
- C27C (p.Cys27Cys), gnomAD 14-20891719-T-C, CADD 2.23
- C27F (p.Cys27Phe), rs140556531, gnomAD 14-20891835-G-T, REVEL 0.49, MetaLR 0.85
- I28F (p.Ile28Phe), gnomAD rs1470487278, Uncertain significance
- I28V (p.Ile28Val), rs1470487278, ClinGen CA351485109, ClinVar RCV004516289, gnomAD rs1470487278, AlphaMissense 0.06, MetaLR 0.20, Uncertain significance, Cardiovascular phenotype
- P30H (p.Pro30His), rs1179404518, ClinGen CA351485095, ClinVar RCV003855669, gnomAD rs1179404518, AlphaMissense 0.63, MetaLR 0.56, Uncertain significance, RASopathy
- P30L (p.Pro30Leu), gnomAD rs1179404518, REVEL 0.03, MetaLR 0.03, Uncertain significance
- P30R (p.Pro30Arg), gnomAD rs1179404518, Uncertain significance
- P30S (p.Pro30Ser), rs765857063, ClinGen CA2259840, ClinVar RCV002047618, ClinVar RCV004988790, REVEL 0.01, MetaLR 0.02, Uncertain significance, Cardiovascular phenotype; RASopathy
- P30P (p.Pro30Pro), gnomAD 14-20891695-A-G, CADD 7.38
- P30T (p.Pro30Thr), gnomAD 14-20891771-C-A, REVEL 0.07, MetaLR 0.06
- P30A (p.Pro30Ala), gnomAD 14-20891774-C-G, REVEL 0.02, MetaLR 0.03
- T31A (p.Thr31Ala), rs1486365900, ClinGen CA351485091, ClinVar RCV001949003, ClinVar RCV002370573, AlphaMissense 0.13, MetaLR 0.28, Uncertain significance, Cardiovascular phenotype; RASopathy
- T31P (p.Thr31Pro), cosmic curated COSV52584, gnomAD rs1486365900, Uncertain significance
- T31R (p.Thr31Arg), Ensembl rs2059450637
- T31N (p.Thr31Asn), rs749108905, gnomAD 14-20891782-T-TA, CADD 19.30
- T31M (p.Thr31Met), rs371809756, gnomAD 14-20891784-C-T, REVEL 0.26, MetaLR 0.57
- T31T (p.Thr31Thr), rs759859690, gnomAD 14-20891785-G-A, CADD 0.17
- I32V (p.Ile32Val), rs372738063, ClinGen CA241481, cosmic curated COSV10586, ClinVar RCV000159060, AlphaMissense 0.06, MetaLR 0.21, Benign, Noonan syndrome and Noonan-related syndrome
- I32M (p.Ile32Met), rs767807631, gnomAD 14-20891806-C-G, REVEL 0.26, MetaLR 0.46
- I32F (p.Ile32Phe), rs760867669, gnomAD 14-20891813-A-T, REVEL 0.22, MetaLR 0.43
- I32N (p.Ile32Asn), rs144042562, gnomAD 14-20891814-T-A, REVEL 0.22, MetaLR 0.54
- I32I (p.Ile32Ile), gnomAD 14-20891815-C-T, CADD 0.48
- V33I (p.Val33Ile), rs1575600440, ClinGen CA351485080, ClinVar RCV000792633, ClinVar RCV002386380, AlphaMissense 0.07, MetaLR 0.26, Uncertain significance, Cardiovascular phenotype; RASopathy
- Q34* (p.Gln34Ter), Ensembl rs2125453261
- Q34L (p.Gln34Leu), ExAC rs769429487, gnomAD rs769429487
- Q34R (p.Gln34Arg), ExAC rs769429487, gnomAD rs769429487
- Q34Q (p.Gln34Gln), rs1877563300, gnomAD 14-20891779-G-A, CADD 0.28
- Q35H (p.Gln35His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q35R (p.Gln35Arg), TOPMed rs1286819839, gnomAD rs1286819839
- Q35Q (p.Gln35Gln), gnomAD 14-20891794-G-A, CADD 1.46
- F36V (p.Phe36Val), rs2125453209, ClinGen CA351485057, ClinVar RCV001368161, Ensembl rs2125453209, AlphaMissense 0.20, MetaLR 0.26, Uncertain significance, RASopathy
- F36L (p.Phe36Leu), rs770621900, gnomAD 14-20891797-GT-G, CADD 24.10
- G37D (p.Gly37Asp), Ensembl rs2125453193
- Y38C (p.Tyr38Cys), rs576041742, ClinGen CA351485043, ClinVar RCV003118149, 1000Genomes rs576041742, AlphaMissense 0.08, MetaLR 0.19, Likely benign, RASopathy
- Y38H (p.Tyr38His), ExAC rs747783742, gnomAD rs747783742
- Y38S (p.Tyr38Ser), rs576041742, ClinGen CA2259836, ClinVar RCV000619923, ClinVar RCV000811009, AlphaMissense 0.08, MetaLR 0.19, Conflicting interpretations, Noonan syndrome and Noonan-related syndrome; Cardiovascular phenotype; RASopathy
- Y38D (p.Tyr38Asp), rs1400166609, gnomAD 14-20891864-T-G, REVEL 0.15, MetaLR 0.16
- Y38F (p.Tyr38Phe), gnomAD 14-20891865-A-T, REVEL 0.09, MetaLR 0.06
- Y38Y (p.Tyr38Tyr), rs753815870, gnomAD 14-20891866-T-C, CADD 0.16
- Q39* (p.Gln39Ter), TOPMed rs2059449698
- Q39E (p.Gln39Glu), cosmic curated COSV99312, TOPMed rs2059449698
- R40C (p.Arg40Cys), rs772390935, ClinGen CA2259835, NCI-TCGA Cosmic COSV5258, cosmic curated COSV52583, AlphaMissense 0.32, MetaLR 0.47, Likely benign, RASopathy
- R40H (p.Arg40His), rs192632236, ClinGen CA201617, ClinVar RCV000127704, ClinVar RCV000175738, AlphaMissense 0.22, MetaLR 0.22, Benign, RASopathy
- R40L (p.Arg40Leu), 1000Genomes rs192632236, ExAC rs192632236, TOPMed rs192632236, gnomAD rs192632236, Uncertain significance, Cardiovascular phenotype
- R40K (p.Arg40Lys), gnomAD 14-20891787-G-A, REVEL 0.12, MetaLR 0.14
- R41G (p.Arg41Gly), TOPMed rs1480507957, Uncertain significance
- R41L (p.Arg41Leu), rs145611571, ClinGen CA2259834, ClinVar RCV000406219, ClinVar RCV000530532, AlphaMissense 0.54, MetaLR 0.32, Conflicting interpretations, not provided; RASopathy; Cardiovascular phenotype
- R41Q (p.Arg41Gln), rs145611571, ClinGen CA134693, cosmic curated COSV10605, ClinVar RCV000037673, AlphaMissense 0.54, MetaLR 0.32, Conflicting interpretations, Noonan syndrome and Noonan-related syndrome; Cardiovascular phenotype; not speci
- R41W (p.Arg41Trp), rs1480507957, ClinGen CA351485027, NCI-TCGA Cosmic COSV5257, cosmic curated COSV52577, AlphaMissense 0.54, MetaLR 0.28, Uncertain significance, not provided; RASopathy
- R41S (p.Arg41Ser), rs1393494732, gnomAD 14-20891823-A-AC, CADD 0.10
- R41* (p.Arg41Ter), rs1877565766, gnomAD 14-20891831-C-T, CADD 26.40
- R41P (p.Arg41Pro), gnomAD 14-20891832-G-C, REVEL 0.35, MetaLR 0.27
- A42I (p.Ala42Ile), rs876657965, ClinGen CA10576608, ClinVar RCV000219930, ClinVar RCV000461796, Likely benign, RASopathy
- A42P (p.Ala42Pro), ExAC rs200856000, TOPMed rs200856000, gnomAD rs200856000, Benign
- A42T (p.Ala42Thr), rs200856000, ClinGen CA2259833, ClinVar RCV000522560, ClinVar RCV000981699, AlphaMissense 0.14, MetaLR 0.24, Likely benign, RASopathy
- A42V (p.Ala42Val), rs11549992, ClinGen CA2259832, ClinVar RCV000290750, ClinVar RCV000398939, AlphaMissense 0.14, MetaLR 0.23, Likely benign, RASopathy
- A42E (p.Ala42Glu), rs1877563677, gnomAD 14-20891784-C-CGA, CADD 20.40
- A42A (p.Ala42Ala), gnomAD 14-20891791-T-C, CADD 7.84
- A42D (p.Ala42Asp), gnomAD 14-20891802-C-A, REVEL 0.19, MetaLR 0.21
- S43L (p.Ser43Leu), Ensembl rs2125453053
- S43R (p.Ser43Arg), rs749325429, gnomAD 14-20891816-A-C, REVEL 0.03, MetaLR 0.03
- D44A (p.Asp44Ala), rs756420598, ClinGen CA351485011, ClinVar RCV003832955, ExAC rs756420598, AlphaMissense 0.38, MetaLR 0.25, Uncertain significance, RASopathy
- D44E (p.Asp44Glu), rs2470447219, ClinGen CA351485009, ClinVar RCV002829368, Uncertain significance, RASopathy
- D44N (p.Asp44Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D44V (p.Asp44Val), ExAC rs756420598, gnomAD rs756420598, Uncertain significance
- D45N (p.Asp45Asn), rs1575600313, ClinGen CA351485007, ClinVar RCV000795085, Ensembl rs1575600313, AlphaMissense 0.20, MetaLR 0.38, Uncertain significance, RASopathy
- G46A (p.Gly46Ala), Ensembl rs2125453017
- G46D (p.Gly46Asp), cosmic curated COSV99313, Ensembl rs2125453017
- L48F (p.Leu48Phe), cosmic curated COSV52586, ExAC rs752967378, gnomAD rs752967378, Uncertain significance, RASopathy
- L48V (p.Leu48Val), rs752967378, ClinGen CA10587562, ClinVar RCV000242585, ExAC rs752967378, AlphaMissense 0.08, MetaLR 0.16, Uncertain significance, Cardiovascular phenotype
- L48L (p.Leu48Leu), rs755183918, gnomAD 14-20891699-C-T, CADD 2.04
- L48P (p.Leu48Pro), rs1272043183, gnomAD 14-20891730-T-C, REVEL 0.12, MetaLR 0.07
- L48R (p.Leu48Arg), gnomAD 14-20891739-T-G, REVEL 0.22, MetaLR 0.07
- T49I (p.Thr49Ile), Ensembl rs2125452958
- T49R (p.Thr49Arg), rs2125452958, ClinGen CA351484977, ClinVar RCV002303341, AlphaMissense 0.09, MetaLR 0.21, Uncertain significance, RASopathy
- T49N (p.Thr49Asn), rs774318039, gnomAD 14-20891838-C-A, REVEL 0.03, MetaLR 0.02
- D50V (p.Asp50Val), ExAC rs767460388, gnomAD rs767460388
- D50Y (p.Asp50Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P51A (p.Pro51Ala), rs2470446970, ClinGen CA351484968, ClinVar RCV003868673, Uncertain significance, RASopathy
- P51T (p.Pro51Thr), rs1230787360, gnomAD 14-20891825-C-A, REVEL 0.16, MetaLR 0.22
- P51P (p.Pro51Pro), gnomAD 14-20891827-C-G, CADD 0.15
- P51S (p.Pro51Ser), rs202232277, gnomAD 14-20891828-C-T, REVEL 0.09, MetaLR 0.16
- P51H (p.Pro51His), rs200170777, gnomAD 14-20891829-C-A, REVEL 0.11, MetaLR 0.20
- P51L (p.Pro51Leu), rs200170777, gnomAD 14-20891829-C-T, REVEL 0.06, MetaLR 0.12
- P51R (p.Pro51Arg), rs200170777, gnomAD 14-20891829-C-G, REVEL 0.14, MetaLR 0.16
- S52A (p.Ser52Ala), TOPMed rs2059448160, gnomAD rs2059448160
- S52F (p.Ser52Phe), Ensembl rs150548390
- S52P (p.Ser52Pro), TOPMed rs2059448160, gnomAD rs2059448160
- T54I (p.Thr54Ile), ExAC rs754798801, TOPMed rs754798801, gnomAD rs754798801, Likely benign, RASopathy
- T54K (p.Thr54Lys), rs754798801, ClinGen CA351484946, ClinVar RCV002204537, ExAC rs754798801, AlphaMissense 0.18, MetaLR 0.28, Uncertain significance, Dilated cardiomyopathy 1NN; LEOPARD syndrome 2; Noonan syndrome 5
- S55I (p.Ser55Ile), gnomAD rs1375650636
- S55N (p.Ser55Asn), gnomAD rs1375650636
- S55R (p.Ser55Arg), TOPMed rs897009059, gnomAD rs897009059
- N56H (p.Asn56His), gnomAD rs1417918204
- N56N (p.Asn56Asn), rs142084658, gnomAD 14-20891824-C-T, CADD 0.04
- N56K (p.Asn56Lys), rs142084658, gnomAD 14-20891824-C-A, REVEL 0.14, MetaLR 0.23
- N56D (p.Asn56Asp), gnomAD 14-20891861-A-G, REVEL 0.04, MetaLR 0.06
- N56S (p.Asn56Ser), gnomAD 14-20891862-A-G, REVEL 0.04, MetaLR 0.05
- T57A (p.Thr57Ala), TOPMed rs141658044, Uncertain significance, Cardiovascular phenotype; RASopathy
- T57I (p.Thr57Ile), gnomAD rs1180734177
- T57P (p.Thr57Pro), TOPMed rs141658044, Uncertain significance
- I58F (p.Ile58Phe), Ensembl rs147984543, Uncertain significance
- I58L (p.Ile58Leu), Ensembl rs147984543, Uncertain significance, not specified
- I58V (p.Ile58Val), rs759443996, gnomAD 14-20891840-A-G, REVEL 0.03, MetaLR 0.15
- I58T (p.Ile58Thr), rs1877566139, gnomAD 14-20891841-T-C, REVEL 0.07, MetaLR 0.14
- I58I (p.Ile58Ile), gnomAD 14-20891842-T-C, CADD 3.29
- R59C (p.Arg59Cys), cosmic curated COSV52574, gnomAD rs2059446969, Uncertain significance, RASopathy
- R59H (p.Arg59His), rs1559447623, ClinGen CA351484917, NCI-TCGA Cosmic COSV9931, cosmic curated COSV99312, AlphaMissense 0.91, MetaLR 0.38, Uncertain significance, not provided; Noonan syndrome; RASopathy
- R59P (p.Arg59Pro), Ensembl rs1559447623, Uncertain significance
- R59W (p.Arg59Trp), rs115812876, gnomAD 14-20891849-C-T, REVEL 0.31, MetaLR 0.55
- R59R (p.Arg59Arg), rs115812876, gnomAD 14-20891849-C-A, CADD 0.22
- R59Q (p.Arg59Gln), rs760744021, gnomAD 14-20891850-G-A, REVEL 0.09, MetaLR 0.15
- R59G (p.Arg59Gly), rs183860442, gnomAD 14-20891867-C-G, REVEL 0.13, MetaLR 0.03
- R59* (p.Arg59Ter), rs183860442, gnomAD 14-20891867-C-T, CADD 23.70
Public RAF1 analysis runs
- RAF1 analysis run — RAF1 (2,086 variants) — completed 2026-08-19