Is BRAF p.Pro403fs (c.1208del) pathogenic?

BRAF p.Pro403fs (c.1208del) is classified Uncertain significance in BRAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-30). Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with BRAF p.Pro403fs (c.1208del)?

BRAF p.Pro403fs (c.1208del) is associated with RASopathy (ClinVar).

How common is BRAF p.Pro403fs (c.1208del) in the general population?

BRAF p.Pro403fs (c.1208del) is absent from gnomAD v4.1 (gnomAD).

BRAF p.Pro403fs

c.1208del · rs777474487 · VCV2077036

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,998)

Conditions

RASopathy

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 10 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP 0.79, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,998). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRAF
Protein: p.Pro403fs
Coding: c.1208del
MANE Select: NM_004333
dbSNP: rs777474487
Type: Deletion
Location: chr7:140783127 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 403: the 'disordered' region

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.Pro403Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRAF p.Pro403Thr Uncertain significance ★ ⚠ same residue
BRAF p.Ala404fs Uncertain significance ★★ same condition
BRAF c.139-9del Likely benign ★★ same condition
BRAF c.2128-16_2128-7del Benign/Likely benign ★★ same condition
BRAF c.2128-27_2128-19del Likely benign ★★ same condition
BRAF c.2128-5del Benign/Likely benign ★★ same condition
BRAF c.138+6_138+11del Uncertain significance ★ 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-pro403fs (accessed [today's date]).

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