Is BRCA1 p.Asp1778= (c.5334T>C) pathogenic?

BRCA1 p.Asp1778= (c.5334T>C) is classified Benign/Likely benign in BRCA1 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-01-19). Very rare (popmax 0.00271%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA1 p.Asp1778= (c.5334T>C)?

BRCA1 p.Asp1778= (c.5334T>C) is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Asp1778= (c.5334T>C) in the general population?

BRCA1 p.Asp1778= (c.5334T>C) is very rare (popmax 0.00271%, nfe) (gnomAD).

BRCA1 p.Asp1778=

c.5334T>C · rs754152768 · VCV186289

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00271%, 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 7	GERP 2.8, phastCons 1
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,852 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,613,854 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,870
Admixed American	0.00167%	59,998
African / African-American	0.00133%	74,920

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.Asp1778=
Coding: c.5334T>C
MANE Select: NM_007294
dbSNP: rs754152768
Type: single nucleotide variant
Location: chr17:43049193 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1778: a UniProt-annotated variant site (in fancs); the brct 2 domain; 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 breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome

Similar variants

BRCA1 p.Asp1778Asn Pathogenic ★★★ ⚠ same residue
BRCA1 p.Asp1778Glu Uncertain significance ★★ ⚠ same residue
BRCA1 p.Asp1778Tyr Likely pathogenic ★ ⚠ same residue
BRCA1 p.Asp1778Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp1778His Conflicting classifications of pathogenicity ★ ⚠ 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

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-asp1778 (accessed [today's date]).

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