Is BRCA2 p.Ala2864del (c.8590_8592del) pathogenic?

BRCA2 p.Ala2864del (c.85908592del) is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-17). Very rare (popmax 0.00167%, amr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Ala2864del (c.8590_8592del)?

BRCA2 p.Ala2864del (c.8590_8592del) is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ala2864del (c.8590_8592del) in the general population?

BRCA2 p.Ala2864del (c.8590_8592del) is very rare (popmax 0.00167%, amr) (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.

BRCA2 p.Ala2864del

c.8590_8592del · rs1555287779 · VCV462485

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 4.2	GERP -1.4, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,032 alleles

Overall 0.000137% 2/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,032
European (non-Finnish)	8.47e-05%	1,180,004

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: BRCA2
Protein: p.Ala2864del
Coding: c.8590_8592del
MANE Select: NM_000059
dbSNP: rs1555287779
Type: Deletion
Location: chr13:32371058 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

Full BRCA2 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

Also linked: hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ala2864fs Pathogenic ★ same residue
BRCA2 p.Ala2864Val Uncertain significance ★★ ⚠ same residue
BRCA2 p.Ala2864Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala2864Ser Uncertain significance ★ ⚠ same residue
BRCA2 p.Ala2864Thr Uncertain significance ★ ⚠ same residue
BRCA2 p.Ala2864= Likely benign ★ same residue
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del 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/brca2-p-ala2864del (accessed [today's date]).

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