Is BRCA1 p.Val1532= (c.4596T>C) pathogenic?

BRCA1 p.Val1532= (c.4596T>C) is classified Likely benign in BRCA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-11). Very rare (popmax 0.000254%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Val1532= (c.4596T>C)?

BRCA1 p.Val1532= (c.4596T>C) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Val1532= (c.4596T>C) in the general population?

BRCA1 p.Val1532= (c.4596T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

BRCA1 p.Val1532=

c.4596T>C · rs1567777953 · VCV628947

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

hereditary neoplastic syndrome

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 0.31	GERP -3
Overall
CADD	2.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,036 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,178 alleles · very rare exomes 3/1,461,858 · genomes 0/152,320 · 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: BRCA1
Protein: p.Val1532=
Coding: c.4596T>C
MANE Select: NM_007294
dbSNP: rs1567777953
Type: single nucleotide variant
Location: chr17:43074410 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1532: a UniProt-annotated variant site (in fancs)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1

Similar variants

BRCA1 p.Val1532Ala Uncertain significance ★★ ⚠ same residue
BRCA1 p.Val1532Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Val1532fs Pathogenic ★★★ same residue
BRCA1 p.Val1532del Uncertain significance ★★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T Pathogenic ★★★ same condition
BRCA1 c.212+1G>A Pathogenic ★★★ same condition
BRCA1 c.212+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-val1532 (accessed [today's date]).

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