Is BRAF p.Leu711= (c.2133C>T) pathogenic?

BRAF p.Leu711= (c.2133C>T) is classified Likely benign in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Very rare (popmax 0.000331%, nfe); Associated with RASopathy.

What condition is associated with BRAF p.Leu711= (c.2133C>T)?

BRAF p.Leu711= (c.2133C>T) is associated with RASopathy (ClinVar).

How common is BRAF p.Leu711= (c.2133C>T) in the general population?

BRAF p.Leu711= (c.2133C>T) is very rare (popmax 0.000331%, nfe) (gnomAD).

BRAF p.Leu711=

c.2133C>T · rs2130869623 · VCV1567261

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000331%, nfe)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.021	GERP -0.93, phastCons 0.2
Overall
CADD	7.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000331% European (non-Finnish) · 3/906,644 alleles

Filtering AF 8.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.4e-05%

Overall 0.000279% 3/1,075,768 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRAF
Protein: p.Leu711=
Coding: c.2133C>T
MANE Select: NM_004333
dbSNP: rs2130869623
Type: single nucleotide variant
Location: chr7:140734765 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 711: an α-helix; the protein kinase domain

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

Disease context

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

Similar variants

BRAF p.Leu711Phe Uncertain significance ★ ⚠ same residue
BRAF p.Leu711Pro Likely pathogenic ★ 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.Gly265Arg 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-leu711 (accessed [today's date]).

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