RAF1 p.Val263=
c.789C>G · rs1308245149 · VCV1140514
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.4 | GERP -2.4, phastCons 0.98 |
| Overall | ||
| CADD | 6.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,180,036 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,614,180 alleles · very rare
exomes 3/1,461,878 · genomes 0/152,302 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- RAF1
- Protein
- p.Val263=
- Coding
- c.789C>G
- MANE Select
- NM_002880
- dbSNP
- rs1308245149
- Type
- single nucleotide variant
- Location
- chr3:12604181 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.24 · 76 PDB
- Residue 263
- the 'disordered' region; a UniProt-annotated variant site (in ns5; shows in vitro greater kinase activity and enhanced mapk1 activation than wild-type)
Similar variants
- RAF1 p.Val263Gly Likely pathogenic ★★★ ⚠ same residue
- RAF1 p.Val263Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Val263Asp Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Arg256Ser Likely pathogenic ★★★ ⚠ same condition
- RAF1 p.Gly361Ala Pathogenic ★★★ ⚠ same condition
- RAF1 p.Leu613Val Pathogenic ★★★ same condition
- RAF1 p.Pro261Ser Pathogenic ★★★ ⚠ same condition
- RAF1 p.Ser257Leu Pathogenic ★★★ ⚠ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/raf1-p-val263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown