Is BRAF p.Ile714Val (c.2140A>G) pathogenic?

BRAF p.Ile714Val (c.2140A>G) is classified Uncertain significance in BRAF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-15). AlphaMissense: likely benign (0.1154); Very rare (popmax 0.00166%, sas); Associated with melanoma, cutaneous malignant, susceptibility to, 1.

What condition is associated with BRAF p.Ile714Val (c.2140A>G)?

BRAF p.Ile714Val (c.2140A>G) is associated with melanoma, cutaneous malignant, susceptibility to, 1, colorectal cancer, cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Ile714Val (c.2140A>G) in the general population?

BRAF p.Ile714Val (c.2140A>G) is very rare (popmax 0.00166%, sas) (gnomAD).

What do computational predictors say about BRAF p.Ile714Val (c.2140A>G)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

BRAF p.Ile714Val

c.2140A>G · rs555976452 · VCV1410272

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00166%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

melanoma, cutaneous malignant, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.661	pathogenic-leaning
SaProt	LLR -6.16	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 4, phastCons 1
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00166% South Asian · 1/60,244 alleles

Filtering AF 0.000598% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000472%

Overall 0.000934% 13/1,391,426 alleles · very rare exomes 10/1,312,956 · genomes 3/78,470 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00166%	60,244
European (non-Finnish)	0.00112%	89,177

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.Ile714Val
Coding: c.2140A>G
MANE Select: NM_004333
dbSNP: rs555976452
Type: single nucleotide variant
Location: chr7:140734758 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 714: an α-helix; the protein kinase domain

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 Noonan syndrome 1 lung cancer Noonan syndrome 7 LEOPARD syndrome 3 RASopathy

Similar variants

BRAF p.Ile714= Likely benign ★ 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
BRAF p.Gly464Glu 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-ile714val (accessed [today's date]).

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