Is BRCA1 p.His1673del (c.5014CAC[1]) pathogenic?

BRCA1 p.His1673del (c.5014CAC[1]) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2025-11-26). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.His1673del (c.5014CAC[1])?

BRCA1 p.His1673del (c.5014CAC[1]) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.His1673del (c.5014CAC[1]) in the general population?

BRCA1 p.His1673del (c.5014CAC[1]) is absent from gnomAD (gnomAD).

BRCA1 p.His1673del

c.5014CAC[1] · rs80358343 · VCV55355

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP -0.22	GERP -3.3

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA1
Protein: p.His1673del
Coding: c.5014CAC[1]
MANE Select: NM_007294
dbSNP: rs80358343
Type: Microsatellite
Location: chr17:43067663 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1673: the brct 1 domain; 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.His1673fs Pathogenic ★★★ same residue
BRCA1 p.His1673= Likely benign ★★ same residue
BRCA1 p.His1673Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.His1673Asp Likely benign ★ same residue
BRCA1 p.His1673Tyr Likely benign ★ ⚠ same residue
BRCA1 p.Ala1082_Met1083insTer Pathogenic ★★★ same condition
BRCA1 p.Ala92fs Pathogenic ★★★ same condition
BRCA1 p.Arg1583fs 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-his1673del (accessed [today's date]).

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