Is BRCA1 p.Glu85del (c.252_254del) pathogenic?

BRCA1 p.Glu85del (c.252254del) is classified Uncertain significance in BRCA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-03). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Glu85del (c.252_254del)?

BRCA1 p.Glu85del (c.252_254del) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Glu85del (c.252_254del) in the general population?

BRCA1 p.Glu85del (c.252_254del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

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.Glu85del

c.252_254del · rs1064797221 · VCV425132

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary breast ovarian cancer 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 0.12	GERP -0.17, phastCons 0.93

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,992 alleles

Overall 6.84e-05% 1/1,461,642 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.Glu85del
Coding: c.252_254del
MANE Select: NM_007294
dbSNP: rs1064797221
Type: Deletion
Location: chr17:43104915 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 85: an α-helix

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.Glu85= Likely benign ★★★ same residue
BRCA1 p.Glu85Lys Uncertain significance ★★ ⚠ same residue
BRCA1 p.Glu85Asp Conflicting classifications of pathogenicity ★ ⚠ 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
BRCA1 c.5277+1_5277+6del Pathogenic ★★★ same condition
BRCA1 c.5278-2del 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-glu85del (accessed [today's date]).

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