Is BRCA1 p.Asn1678fs (c.5032_5033del) pathogenic?

BRCA1 p.Asn1678fs (c.50325033del) is classified Likely pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Asn1678fs (c.5032_5033del)?

BRCA1 p.Asn1678fs (c.5032_5033del) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA1 p.Asn1678fs

c.5032_5033del · VCV4082387

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 16 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -0.7, phastCons 0.004

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BRCA1
Protein: p.Asn1678fs
Coding: c.5032_5033del
MANE Select: NM_007294
Type: Deletion
Location: chr17:43067649 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1678: the brct 1 domain; a UniProt-annotated variant site (in fancs); a β-strand

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

Disease context

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

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Asn1678_Leu1679insTer Pathogenic ★★★ same residue
BRCA1 p.Asn1678= Likely benign ★★ same residue
BRCA1 p.Asn1678Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asn1678Ser Uncertain significance ★ ⚠ same residue
BRCA1 p.Asn1678Tyr Uncertain significance ★ ⚠ same residue
BRCA1 c.302-2del Pathogenic ★★★ same condition
BRCA1 c.442-22_442-13del Pathogenic ★★★ same condition
BRCA1 c.4484+1del 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-asn1678fs (accessed [today's date]).

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