Is BRAF p.Cys264fs (c.789_790del) pathogenic?

BRAF p.Cys264fs (c.789790del) is classified Uncertain significance in BRAF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-15). Very rare (popmax 0.00017%, nfe); Associated with cardiofaciocutaneous syndrome 1.

What condition is associated with BRAF p.Cys264fs (c.789_790del)?

BRAF p.Cys264fs (c.789_790del) is associated with cardiofaciocutaneous syndrome 1 (ClinVar).

How common is BRAF p.Cys264fs (c.789_790del) in the general population?

BRAF p.Cys264fs (c.789_790del) is very rare (popmax 0.00017%, nfe) (gnomAD).

BRAF p.Cys264fs

c.789_790del · rs1803104915 · VCV931893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

cardiofaciocutaneous syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 3.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,936 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,712 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.Cys264fs
Coding: c.789_790del
MANE Select: NM_004333
dbSNP: rs1803104915
Type: Deletion
Location: chr7:140801482 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 264: a turn; a binding site

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 c.2128-27_2128-19del Likely benign ★★ same condition
BRAF p.Pro492del Likely pathogenic ★ same condition
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
BRAF p.Gly596Val 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-cys264fs (accessed [today's date]).

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