Is BRAF p.Asp40Ala (c.119A>C) pathogenic?

BRAF p.Asp40Ala (c.119A>C) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). AlphaMissense: likely benign (0.1745); Very rare (popmax 7.3e-05%); Associated with Cardiovascular phenotype.

What condition is associated with BRAF p.Asp40Ala (c.119A>C)?

BRAF p.Asp40Ala (c.119A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is BRAF p.Asp40Ala (c.119A>C) in the general population?

BRAF p.Asp40Ala (c.119A>C) is very rare (popmax 7.3e-05%) (gnomAD).

What do computational predictors say about BRAF p.Asp40Ala (c.119A>C)?

AlphaMissense predicts likely benign (score 0.1745) — an in-silico prediction, not a clinical call.

BRAF p.Asp40Ala

c.119A>C · rs1818656083 · VCV2394545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.3e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1745	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -4.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.4, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.3e-05%

Overall 7.3e-05% 1/1,369,806 alleles · very rare

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.Asp40Ala
Coding: c.119A>C
MANE Select: NM_004333
dbSNP: rs1818656083
Type: single nucleotide variant
Location: chr7:140924585 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB

Full BRAF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp40ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown