Is BRCA1 p.Glu765= (c.2295G>A) pathogenic?

BRCA1 p.Glu765= (c.2295G>A) is classified Likely benign in BRCA1 (ClinVar, Expert panel, 7 submitters; last evaluated 2017-06-29). Very rare (popmax 0.00446%, eas); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Glu765= (c.2295G>A)?

BRCA1 p.Glu765= (c.2295G>A) is associated with breast-ovarian cancer, familial, susceptibility to, 1, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA1 p.Glu765= (c.2295G>A) in the general population?

BRCA1 p.Glu765= (c.2295G>A) is very rare (popmax 0.00446%, eas) (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.Glu765=

c.2295G>A · rs201875054 · VCV185582

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

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 -0.22	GERP -3.1, phastCons 0.15
Overall
CADD	2.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00031% 5/1,614,076 alleles · very rare exomes 2/1,461,756 · genomes 3/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,440
African / African-American	0.00266%	37,526
European (non-Finnish)	8.47e-05%	1,179,986

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.Glu765=
Coding: c.2295G>A
MANE Select: NM_007294
dbSNP: rs201875054
Type: single nucleotide variant
Location: chr17:43093236 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

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

Disease context

breast-ovarian cancer, familial, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast cancer hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Glu765Ter Pathogenic ★★★ same residue
BRCA1 p.Glu765Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Glu765Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Glu765Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Glu765_Ser766insTer Pathogenic ★★★ same residue
BRCA1 p.Glu765fs Pathogenic ★ same residue
BRCA1 p.Glu765_Ser766insArg Uncertain significance ★ same residue
BRCA1 p.Glu765Lys Uncertain significance ★ ⚠ same residue

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-glu765 (accessed [today's date]).

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