Is BRAF p.Thr241Pro (c.721A>C) pathogenic?

BRAF p.Thr241Pro (c.721A>C) is classified Pathogenic/Likely pathogenic in BRAF (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.9968); Absent from gnomAD v4.1; Associated with cardiofaciocutaneous syndrome.

What condition is associated with BRAF p.Thr241Pro (c.721A>C)?

BRAF p.Thr241Pro (c.721A>C) is associated with cardiofaciocutaneous syndrome, lung carcinoma, cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Thr241Pro (c.721A>C) in the general population?

BRAF p.Thr241Pro (c.721A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRAF p.Thr241Pro (c.721A>C)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

BRAF p.Thr241Pro

c.721A>C · rs387906661 · VCV29807

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiofaciocutaneous syndrome

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic ✓ concordant with ClinVar
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -13.05	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 7.8	GERP 3.5, phastCons 1
Overall
CADD	28.8	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.Thr241Pro
Coding: c.721A>C
MANE Select: NM_004333
dbSNP: rs387906661
Type: single nucleotide variant
Location: chr7:140801551 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 241: a β-strand; a UniProt-annotated variant site (in ns7); a UniProt-annotated variant site (in cfc1 and lprd3)

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

Also linked: lung carcinoma cardiofaciocutaneous syndrome 1 Noonan syndrome with multiple lentigines Noonan syndrome 1 Noonan syndrome 7 LEOPARD syndrome 3 RASopathy

Similar variants

BRAF p.Thr241Lys Pathogenic ★★★ same residue
BRAF p.Thr241Arg Pathogenic ★★ same residue
BRAF p.Thr241Met Pathogenic/Likely pathogenic ★★ same residue
BRAF p.Thr241= Benign/Likely benign ★★ same residue
BRAF p.Thr241Ala Pathogenic ★ same residue
BRAF p.Ala246Pro Pathogenic ★★★ same condition
BRAF p.Asn581Asp Pathogenic ★★★ same condition
BRAF p.Asp594Val 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-thr241pro (accessed [today's date]).

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