RAF1 p.His369=
c.1107C>T · rs761947194 · VCV852175
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
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 -4.7 | GERP -5.5 |
| Overall | ||
| CADD | 0.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,074 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.0036%
58/1,612,276 alleles · ultra-rare
exomes 49/1,460,172 · genomes 9/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,074 |
| South Asian | 0.0154% | 6,503 |
| Admixed American | 0.015% | 6,666 |
| African / African-American | 0.00401% | 24,951 |
| European (non-Finnish) | 0.00238% | 42,088 |
| East Asian | 0.00223% | 44,886 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,420 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
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.His369=
- Coding
- c.1107C>T
- MANE Select
- NM_002880
- dbSNP
- rs761947194
- Type
- single nucleotide variant
- Location
- chr3:12599692 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.24 · 76 PDB
- Residue 369
- a β-strand; the protein kinase domain
Similar variants
- 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
- RAF1 p.Ser259Ala Pathogenic ★★★ ⚠ same condition
- RAF1 p.Ser259Thr 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-his369 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown