RAF1 p.Ser257=
c.771G>A · rs764065991 · VCV1112676
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 -7.9 | GERP -5.5 |
| Overall | ||
| CADD | 4.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,078 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000867%
14/1,614,018 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,216 |
| Finnishnot grpmax-eligible | 0.00312% | 32,010 |
| East Asian | 0.00223% | 44,894 |
| Admixed American | 0.00167% | 59,984 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00133% | 74,922 |
| European (non-Finnish) | 0.000254% | 393,346 |
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.Ser257=
- Coding
- c.771G>A
- MANE Select
- NM_002880
- dbSNP
- rs764065991
- Type
- single nucleotide variant
- Location
- chr3:12604199 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.24 · 76 PDB
- Residue 257
- the 'disordered' region; a UniProt-annotated variant site (in ns5 and lprd2; shows in vitro greater kinase activity and enhanced erk activation than wild-type); an α-helix
Similar variants
- RAF1 p.Ser257Leu Pathogenic ★★★ same residue
- RAF1 p.Ser257Pro Likely pathogenic ★★★ same residue
- RAF1 p.Ser257Thr Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Ser257Trp Conflicting classifications of pathogenicity ★ ⚠ 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
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-ser257 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown