Is BRAF p.Phe19= (c.57C>T) pathogenic?

BRAF p.Phe19= (c.57C>T) is classified Likely benign in BRAF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Very rare (popmax 0.000372%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with BRAF p.Phe19= (c.57C>T)?

BRAF p.Phe19= (c.57C>T) is associated with Cardiovascular phenotype, RASopathy (ClinVar).

How common is BRAF p.Phe19= (c.57C>T) in the general population?

BRAF p.Phe19= (c.57C>T) is very rare (popmax 0.000372%, nfe) (gnomAD).

BRAF p.Phe19=

c.57C>T · rs2536968080 · VCV2975584

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000372%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2, phastCons 1
Overall
CADD	14.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000372% European (non-Finnish) · 4/1,075,528 alleles

Filtering AF 8.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.9e-05%

Overall 0.000275% 4/1,452,570 alleles · very rare exomes 4/1,301,230 · genomes 0/151,340 · joint denominator

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.Phe19=
Coding: c.57C>T
MANE Select: NM_004333
dbSNP: rs2536968080
Type: single nucleotide variant
Location: chr7:140924647 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.87 · 135 PDB
Residue 19: the 'disordered' region

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

Disease context

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

Also linked: RASopathy

Similar variants

BRAF p.Phe19Leu Uncertain significance ★ ⚠ 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
BRAF p.Gly464Glu 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-phe19 (accessed [today's date]).

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