Is BRAF p.Pro341Leu (c.1022C>T) pathogenic?

BRAF p.Pro341Leu (c.1022C>T) is classified Uncertain significance in BRAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-29). AlphaMissense: likely pathogenic (0.6428); Absent from gnomAD v4.1; Associated with cardiofaciocutaneous syndrome 1.

What condition is associated with BRAF p.Pro341Leu (c.1022C>T)?

BRAF p.Pro341Leu (c.1022C>T) is associated with cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Pro341Leu (c.1022C>T) in the general population?

BRAF p.Pro341Leu (c.1022C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Pro341Leu (c.1022C>T)?

AlphaMissense predicts likely pathogenic (score 0.6428) — an in-silico prediction, not a clinical call.

BRAF p.Pro341Leu

c.1022C>T · rs863224722 · VCV449132

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6428 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cardiofaciocutaneous syndrome 1

Computational evidence

Protein change
AlphaMissense	0.6428	likely pathogenic
REVEL	0.448	indeterminate
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.24 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 3.6, phastCons 1
Overall
CADD	32.0	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.

Variant & gene context

Gene: BRAF
Protein: p.Pro341Leu
Coding: c.1022C>T
MANE Select: NM_004333
dbSNP: rs863224722
Type: single nucleotide variant
Location: chr7:140794426 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 341: the 'disordered' region

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

Disease context

cardiofaciocutaneous syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRAF p.Pro341= Conflicting classifications of pathogenicity ★ same residue
BRAF p.Pro341Ala Uncertain significance ★ same residue
BRAF p.Pro341Gln Uncertain significance ★ ⚠ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same condition
BRAF p.Asn581Asp Pathogenic ★★★ same condition
BRAF p.Gln257Arg Pathogenic ★★★ ⚠ same condition
BRAF p.Gly464Glu Pathogenic ★★★ same condition
BRAF p.Gly469Glu 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-pro341leu (accessed [today's date]).

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