Is BRAF p.Ala27= (c.81C>T) pathogenic?

BRAF p.Ala27= (c.81C>T) is classified Likely benign in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). Very rare (popmax 0.00248%, eas); Associated with RASopathy.

What condition is associated with BRAF p.Ala27= (c.81C>T)?

BRAF p.Ala27= (c.81C>T) is associated with RASopathy (ClinVar).

How common is BRAF p.Ala27= (c.81C>T) in the general population?

BRAF p.Ala27= (c.81C>T) is very rare (popmax 0.00248%, eas) (gnomAD).

BRAF p.Ala27=

c.81C>T · rs1330565982 · VCV1086109

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00248%, eas)

Conditions

RASopathy

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 0.57	GERP 1.7, phastCons 1
Overall
CADD	13.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00248% East Asian · 1/40,290 alleles

Overall 0.000197% 3/1,520,716 alleles · very rare exomes 1/1,369,698 · genomes 2/151,018 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00248%	40,290
Admixed American	0.00199%	50,330
European (non-Finnish)	8.79e-05%	1,138,264

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.Ala27=
Coding: c.81C>T
MANE Select: NM_004333
dbSNP: rs1330565982
Type: single nucleotide variant
Location: chr7:140924623 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 27: the 'disordered' region

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

Disease context

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

Similar variants

BRAF p.Ala27Gly Uncertain significance ★★ ⚠ same residue
BRAF p.Ala27Thr Uncertain significance ★★ ⚠ same residue
BRAF p.Ala27Val Uncertain significance ★ ⚠ same residue
BRAF p.Ala27_Ala29del Uncertain significance ★ same residue
BRAF p.Ala27_Gly28insGluAla Uncertain significance ★ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same condition
BRAF p.Asn581Asp Pathogenic ★★★ same condition
BRAF p.Asp594Val 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-ala27 (accessed [today's date]).

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