RAF1 p.Pro261=
c.783T>A · VCV3647548
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 0.053 | GERP -5.5, phastCons 0.19 |
| Overall | ||
| CADD | 6.248 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- RAF1
- Protein
- p.Pro261=
- Coding
- c.783T>A
- MANE Select
- NM_002880
- Type
- single nucleotide variant
- Location
- chr3:12604187 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.24 · 76 PDB
- Residue 261
- the 'disordered' region; a UniProt-annotated variant site (in ns5; shows in vitro greater kinase activity and enhanced mapk1 activation than wild-type); a UniProt-annotated variant site (in ns5; shows greater kinase activity and enhanced mapk1 activation than wild-type); an α-helix
Similar variants
- RAF1 p.Pro261Ser Pathogenic ★★★ ⚠ same residue
- RAF1 p.Pro261Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Pro261Arg Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Pro261His Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Pro261Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Pro261Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RAF1 p.Arg256Ser Likely pathogenic ★★★ ⚠ same condition
- RAF1 p.Gly361Ala 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-pro261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown