Is BRAF p.Ala38Val (c.113C>T) pathogenic?

BRAF p.Ala38Val (c.113C>T) is classified Uncertain significance in BRAF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-08). AlphaMissense: likely benign (0.1007); Very rare (popmax 0.00275%, afr); Associated with melanoma, cutaneous malignant, susceptibility to, 1.

What condition is associated with BRAF p.Ala38Val (c.113C>T)?

BRAF p.Ala38Val (c.113C>T) is associated with melanoma, cutaneous malignant, susceptibility to, 1, colorectal cancer, cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Ala38Val (c.113C>T) in the general population?

BRAF p.Ala38Val (c.113C>T) is very rare (popmax 0.00275%, afr) (gnomAD).

What do computational predictors say about BRAF p.Ala38Val (c.113C>T)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

BRAF p.Ala38Val

c.113C>T · rs886042293 · VCV282044

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00275%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

melanoma, cutaneous malignant, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 2.6, phastCons 1
Overall
CADD	22.1	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 0.00275% African / African-American · 2/72,702 alleles

Filtering AF 0.000457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000171%

Overall 0.000327% 5/1,530,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00275%	36,351
Admixed American	0.00197%	50,778
South Asian	0.00119%	83,858
European (non-Finnish)	8.74e-05%	1,144,628

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.Ala38Val
Coding: c.113C>T
MANE Select: NM_004333
dbSNP: rs886042293
Type: single nucleotide variant
Location: chr7:140924591 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 38: the 'disordered' region

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

Disease context

melanoma, cutaneous malignant, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer cardiofaciocutaneous syndrome 1 lung cancer Noonan syndrome 7 LEOPARD syndrome 3 RASopathy

Similar variants

BRAF p.Ala38Pro Uncertain significance ★★ ⚠ same residue
BRAF p.Ala38Glu Uncertain significance ★ same residue
BRAF p.Ala38Ser Uncertain significance ★ ⚠ same residue
BRAF p.Ala38Thr Uncertain significance ★ ⚠ same residue
BRAF p.Ala38= Likely benign ★ 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-ala38val (accessed [today's date]).

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