Is BRAF p.Ala305= (c.915G>A) pathogenic?

BRAF p.Ala305= (c.915G>A) is classified Conflicting classifications of pathogenicity in BRAF (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-09). Ultra-rare (popmax 0.012%, afr); Associated with Cardiovascular phenotype.

What condition is associated with BRAF p.Ala305= (c.915G>A)?

BRAF p.Ala305= (c.915G>A) is associated with Cardiovascular phenotype, colorectal cancer, cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Ala305= (c.915G>A) in the general population?

BRAF p.Ala305= (c.915G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

BRAF p.Ala305=

c.915G>A · rs145675911 · VCV1091347

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 0.012%, afr)

Conditions

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 2.2	GERP 1.2, phastCons 1
Overall
CADD	13.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,892 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000929% 15/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,321
East Asian	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,346

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.Ala305=
Coding: c.915G>A
MANE Select: NM_004333
dbSNP: rs145675911
Type: single nucleotide variant
Location: chr7:140800427 (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

Also linked: colorectal cancer cardiofaciocutaneous syndrome 1 melanoma, cutaneous malignant, susceptibility to, 1 Noonan syndrome 1 lung cancer Noonan syndrome 7 LEOPARD syndrome 3 RASopathy

Similar variants

BRAF p.Ala305Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRAF p.Ala305Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala305 (accessed [today's date]).

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