Is BRCA2 p.Asp237del (c.708TGA[1]) pathogenic?

BRCA2 p.Asp237del (c.708TGA[1]) is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-05). Very rare (popmax 8.49e-05%, nfe); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Asp237del (c.708TGA[1])?

BRCA2 p.Asp237del (c.708TGA[1]) is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Asp237del (c.708TGA[1]) in the general population?

BRCA2 p.Asp237del (c.708TGA[1]) is very rare (popmax 8.49e-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.

BRCA2 p.Asp237del

c.708TGA[1] · rs876660483 · VCV233551

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.49e-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 -0.022	GERP -0.44

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,430 alleles

Overall 6.85e-05% 1/1,459,696 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: BRCA2
Protein: p.Asp237del
Coding: c.708TGA[1]
MANE Select: NM_000059
dbSNP: rs876660483
Type: Microsatellite
Location: chr13:32330944 (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.Asp237Gly Uncertain significance ★★ ⚠ same residue
BRCA2 p.Asp237Val Uncertain significance ★★ ⚠ same residue
BRCA2 p.Asp237Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp237Tyr Uncertain significance ★ ⚠ same residue
BRCA2 p.Ala1439fs Pathogenic ★★★ same condition
BRCA2 p.Ala1725Ter Pathogenic ★★★ same condition
BRCA2 p.Arg155_Asp156insTer Pathogenic ★★★ same condition
BRCA2 p.Arg2108_Val2109insTer 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-asp237del (accessed [today's date]).

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