BRAF p.Asn412=
c.1236C>T · rs397516888 · VCV44798
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.331 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.27 | GERP -0.2, phastCons 0.36 |
| Overall | ||
| CADD | 10.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,082 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000682%
11/1,613,928 alleles · very rare
exomes 9/1,461,782 · genomes 2/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,541 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.000678% | 147,499 |
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.Asn412=
- Coding
- c.1236C>T
- MANE Select
- NM_004333
- dbSNP
- rs397516888
- Type
- single nucleotide variant
- Location
- chr7:140783099 (GRCh38)
- Gene constraint
- LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.87 · 135 PDB
- Residue 412
- 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-asn412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown