BRAF p.Arg435=
c.1305G>A · rs763771673 · VCV193670
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.105 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.28 | GERP 0.15, phastCons 0.99 |
| Overall | ||
| CADD | 6.319 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,074 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000682%
11/1,613,602 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,358 |
| European (non-Finnish) | 0.000678% | 147,485 |
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
- BRAF
- Protein
- p.Arg435=
- Coding
- c.1305G>A
- MANE Select
- NM_004333
- dbSNP
- rs763771673
- Type
- single nucleotide variant
- Location
- chr7:140783030 (GRCh38)
- Gene constraint
- LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.87 · 135 PDB
- Residue 435
- the 'disordered' region
Similar variants
- BRAF p.Ala246Pro Pathogenic ★★★ same condition
- BRAF p.Asn581Asp Pathogenic ★★★ same condition
- BRAF p.Asp594Val Pathogenic ★★★ same condition
- BRAF p.Cys532Tyr Likely pathogenic ★★★ same condition
- BRAF p.Gln257Arg Pathogenic ★★★ ⚠ same condition
- BRAF p.Gly265Arg Likely pathogenic ★★★ same condition
- BRAF p.Gly464Glu Pathogenic ★★★ same condition
- BRAF p.Gly469Glu 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/braf-p-arg435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown