Is BRAF p.Val600Met (c.1798G>A) pathogenic?

BRAF p.Val600Met (c.1798G>A) is classified Likely pathogenic in BRAF (ClinVar, Single submitter, 2 submitters; last evaluated 2012-05-09). AlphaMissense: likely pathogenic (0.8882); Absent from gnomAD v4.1; Associated with non-small cell lung carcinoma.

What condition is associated with BRAF p.Val600Met (c.1798G>A)?

BRAF p.Val600Met (c.1798G>A) is associated with non-small cell lung carcinoma (ClinVar).

How common is BRAF p.Val600Met (c.1798G>A) in the general population?

BRAF p.Val600Met (c.1798G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Val600Met (c.1798G>A)?

AlphaMissense predicts likely pathogenic (score 0.8882) — an in-silico prediction, not a clinical call.

BRAF p.Val600Met

c.1798G>A · rs121913378 · VCV44815

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8882 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

non-small cell lung carcinoma

Computational evidence

Protein change
AlphaMissense	0.8882	likely pathogenic ✓ concordant with ClinVar
REVEL	0.691	pathogenic-leaning
SaProt	LLR -10.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 6.8, phastCons 1
Overall
CADD	26.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Melanoma	Dabrafenib	C	Sensitivity/Response

Variant & gene context

Gene: BRAF
Protein: p.Val600Met
Coding: c.1798G>A
MANE Select: NM_004333
dbSNP: rs121913378
Type: single nucleotide variant
Location: chr7:140753337 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 600: an α-helix; the protein kinase domain; a UniProt-annotated variant site (in a melanoma cell line; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in crc; also found in sarcoma, metastatic melanoma, ovarian serous carcinoma, pilocytic astrocytoma; somatic mutation; most common mutation; constitutive and elevated kinase activity; efficiently induces cell transformation; suppression of mutation in melanoma causes growth arrest and promotes apoptosis; loss of regulation by pmrt5)

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

Disease context

non-small cell lung carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRAF p.Val600Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRAF p.Val600_Lys601delinsGlu Likely pathogenic ★ same residue
BRAF p.Val600Gly Pathogenic ★★★ same residue
BRAF p.Val600Leu Pathogenic/Likely pathogenic ★★ same residue
BRAF p.Val600= Likely benign ★ same residue
BRAF p.Gly464Val Pathogenic/Likely pathogenic ★★ same condition
BRAF p.Leu597Val Pathogenic ★★ same condition
BRAF p.Asn581Ser 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-val600met (accessed [today's date]).

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