Is BRCA1 p.Asp1757= (c.5271C>T) pathogenic?

BRCA1 p.Asp1757= (c.5271C>T) is classified Likely benign in BRCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-10). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Asp1757= (c.5271C>T)?

BRCA1 p.Asp1757= (c.5271C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Asp1757= (c.5271C>T) in the general population?

BRCA1 p.Asp1757= (c.5271C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

BRCA1 p.Asp1757=

c.5271C>T · rs1597810460 · VCV867300

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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 2.3	GERP 1.4, phastCons 0.97
Overall
CADD	5.663	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,910 alleles

Overall 6.84e-05% 1/1,461,734 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.Asp1757=
Coding: c.5271C>T
MANE Select: NM_007294
dbSNP: rs1597810460
Type: single nucleotide variant
Location: chr17:43057058 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1757: a UniProt-annotated variant site (in fancs); the brct 2 domain; a turn

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

Similar variants

BRCA1 p.Asp1757Glu Uncertain significance ★★ ⚠ same residue
BRCA1 p.Asp1757Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp1757His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp1757Tyr Likely benign ★ ⚠ 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-asp1757 (accessed [today's date]).

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