Is BRCA1 p.Val1719= (c.5157G>A) pathogenic?

BRCA1 p.Val1719= (c.5157G>A) is classified Likely benign in BRCA1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-04-17). Very rare (popmax 0.0011%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA1 p.Val1719= (c.5157G>A)?

BRCA1 p.Val1719= (c.5157G>A) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Val1719= (c.5157G>A) in the general population?

BRCA1 p.Val1719= (c.5157G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

BRCA1 p.Val1719=

c.5157G>A · rs28897697 · VCV136089

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

Breast and/or ovarian cancer

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 0.054	GERP -0.56, phastCons 0.86
Overall
CADD	7.364	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,177,960 alleles

Filtering AF 0.000616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000891% 13/1,459,316 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: BRCA1
Protein: p.Val1719=
Coding: c.5157G>A
MANE Select: NM_007294
dbSNP: rs28897697
Type: single nucleotide variant
Location: chr17:43063369 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1719: the brct 1 domain; a UniProt-annotated variant site (in fancs); an α-helix

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

Similar variants

BRCA1 p.Val1719Ala Uncertain significance ★★ ⚠ same residue
BRCA1 p.Val1719Met Uncertain significance ★★ ⚠ same residue
BRCA1 p.Val1719Gly Likely pathogenic ★ same residue
BRCA1 p.Val1719Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Val1719Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Val1719fs Pathogenic ★★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T 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/brca1-p-val1719 (accessed [today's date]).

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