RAF1 p.Asp486=
c.1458T>C · rs768729966 · VCV1627451
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 0.64 | GERP -5.5, phastCons 0.94 |
| Overall | ||
| CADD | 7.311 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,928 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,613,964 alleles · very rare
exomes 2/1,461,778 · genomes 1/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,464 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
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.Asp486=
- Coding
- c.1458T>C
- MANE Select
- NM_002880
- dbSNP
- rs768729966
- Type
- single nucleotide variant
- Location
- chr3:12585759 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.24 · 76 PDB
- Residue 486
- the protein kinase domain; a UniProt-annotated variant site (in ns5); a UniProt-annotated variant site (in ns5; has reduced or absent kinase activity)
Similar variants
- RAF1 p.Asp486Gly Pathogenic/Likely pathogenic ★★ same residue
- RAF1 p.Asp486Glu 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
- RAF1 p.Ser257Pro Likely 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-asp486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown