Is BRAF p.Pro367Ala (c.1099C>G) pathogenic?

BRAF p.Pro367Ala (c.1099C>G) is classified Likely pathogenic in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.996); Absent from gnomAD v4.1.

How common is BRAF p.Pro367Ala (c.1099C>G) in the general population?

BRAF p.Pro367Ala (c.1099C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Pro367Ala (c.1099C>G)?

AlphaMissense predicts likely pathogenic (score 0.996) — an in-silico prediction, not a clinical call.

BRAF p.Pro367Ala

c.1099C>G · VCV3338728

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.996	likely pathogenic ✓ concordant with ClinVar
REVEL	0.608	indeterminate
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.5, phastCons 1
Overall
CADD	29.8	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.Pro367Ala
Coding: c.1099C>G
MANE Select: NM_004333
Type: single nucleotide variant
Location: chr7:140794349 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 367: an α-helix; the 'disordered' region

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

Similar variants

BRAF p.Ala246Pro Pathogenic ★★★ same type
BRAF p.Asn581Asp Pathogenic ★★★ same type
BRAF p.Asp594Val Pathogenic ★★★ same type
BRAF p.Cys532Tyr Likely pathogenic ★★★ same type
BRAF p.Gln257Arg Pathogenic ★★★ ⚠ same type
BRAF p.Gly265Arg Likely pathogenic ★★★ same type
BRAF p.Gly464Glu Pathogenic ★★★ same type
BRAF p.Gly469Glu Pathogenic ★★★ same type

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-pro367ala (accessed [today's date]).

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