Is BRCA2 p.Asp752Ter (c.2253dup) pathogenic?

BRCA2 p.Asp752Ter (c.2253dup) is classified Pathogenic in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Asp752Ter (c.2253dup)?

BRCA2 p.Asp752Ter (c.2253dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Asp752Ter (c.2253dup) in the general population?

BRCA2 p.Asp752Ter (c.2253dup) is absent from gnomAD (gnomAD).

BRCA2 p.Asp752Ter

c.2253dup · rs2548523500 · VCV1788475

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.4	GERP -4.6

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: BRCA2
Protein: p.Asp752Ter
Coding: c.2253dup
MANE Select: NM_000059
dbSNP: rs2548523500
Type: Duplication
Location: chr13:32336607 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 752: the 'interaction with npm1' region

Full BRCA2 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

Similar variants

BRCA2 p.Asp752= Likely benign ★★★ same residue
BRCA2 p.Asp752Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp752Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp752Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp752His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp752fs Pathogenic ★★★ same residue
BRCA2 p.Ala127fs Pathogenic ★★★ same condition
BRCA2 p.Ala2951fs 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-asp752ter (accessed [today's date]).

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