RAF1 p.Val420=
c.1260G>C · rs2058494487 · VCV1763079
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
1
Cardiovascular phenotype
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 1.8 | GERP 0.77, phastCons 1 |
| Overall | ||
| CADD | 10.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,892 alleles
Overall
6.2e-05%
1/1,613,344 alleles · very rare
exomes 0/1,461,198 · genomes 1/152,146 · 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.Val420=
- Coding
- c.1260G>C
- MANE Select
- NM_002880
- dbSNP
- rs2058494487
- Type
- single nucleotide variant
- Location
- chr3:12590908 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.24 · 76 PDB
- Residue 420
- a β-strand; the protein kinase domain
Similar variants
- RAF1 p.Pro261His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- RAF1 p.Pro261Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- RAF1 c.207+5G>T Uncertain significance ★★ same condition
- RAF1 c.834+4A>C Uncertain significance ★★ same condition
- RAF1 c.-4A>C Uncertain significance ★★ same condition
- RAF1 p.Ala119Val Uncertain significance ★★ ⚠ same condition
- RAF1 p.Ala566Thr Uncertain significance ★★ ⚠ same condition
- RAF1 p.Ala7Gly Uncertain significance ★★ ⚠ 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-val420 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown