BRAF p.Leu4=
c.12G>T · rs1818686945 · VCV2566896
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, afr)
Conditions
1
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 4.1 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 11.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
African / African-American · 2/60,746 alleles
Filtering AF
0.000546%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000204%
Overall
0.000184%
2/1,084,086 alleles · very rare
exomes 1/932,536 · genomes 1/151,550 · joint denominator
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.Leu4=
- Coding
- c.12G>T
- MANE Select
- NM_004333
- dbSNP
- rs1818686945
- Type
- single nucleotide variant
- Location
- chr7:140924692 (GRCh38)
- Gene constraint
- LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.87 · 135 PDB
- Residue 4
- the 'disordered' region
Similar variants
- BRAF p.Asn236Lys Likely pathogenic ★★ same condition
- BRAF p.Gln262Arg Pathogenic/Likely pathogenic ★★ same condition
- BRAF p.Glu501Lys Pathogenic/Likely pathogenic ★★ same condition
- BRAF c.2127+4A>G Uncertain significance ★★ same condition
- BRAF p.Ala27Gly Uncertain significance ★★ ⚠ same condition
- BRAF p.Ala42Ser Uncertain significance ★★ ⚠ same condition
- BRAF p.Arg252Gly Uncertain significance ★★ ⚠ same condition
- BRAF p.Arg384Lys Uncertain significance ★★ ⚠ 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-leu4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown