Is BRAF p.Ser467Ala (c.1399T>G) pathogenic?

BRAF p.Ser467Ala (c.1399T>G) is classified Pathogenic in BRAF (ClinVar, Single submitter, 2 submitters; last evaluated 2016-04-07). AlphaMissense: likely pathogenic (0.8932); Absent from gnomAD v4.1; Associated with cardiofaciocutaneous syndrome.

What condition is associated with BRAF p.Ser467Ala (c.1399T>G)?

BRAF p.Ser467Ala (c.1399T>G) is associated with cardiofaciocutaneous syndrome (ClinVar).

How common is BRAF p.Ser467Ala (c.1399T>G) in the general population?

BRAF p.Ser467Ala (c.1399T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Ser467Ala (c.1399T>G)?

AlphaMissense predicts likely pathogenic (score 0.8932) — an in-silico prediction, not a clinical call.

BRAF p.Ser467Ala

c.1399T>G · rs869025606 · VCV223138

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiofaciocutaneous syndrome

Computational evidence

Protein change
AlphaMissense	0.8932	likely pathogenic ✓ concordant with ClinVar
REVEL	0.82	moderately pathogenic-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.8, phastCons 1
Overall
CADD	25.4	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.

Variant & gene context

Gene: BRAF
Protein: p.Ser467Ala
Coding: c.1399T>G
MANE Select: NM_004333
dbSNP: rs869025606
Type: single nucleotide variant
Location: chr7:140781609 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 467: a binding site; the protein kinase domain; a UniProt-annotated variant site (in cfc1)

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

Disease context

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

Similar variants

BRAF p.Ser467= Likely benign ★★ same residue
BRAF p.Ser467Leu Uncertain significance ★ ⚠ 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.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-ser467ala (accessed [today's date]).

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