Is BRCA2 p.Ile2552= (c.7656T>A) pathogenic?

BRCA2 p.Ile2552= (c.7656T>A) is classified Likely benign in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-04). Very rare (popmax 0.00446%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ile2552= (c.7656T>A)?

BRCA2 p.Ile2552= (c.7656T>A) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ile2552= (c.7656T>A) in the general population?

BRCA2 p.Ile2552= (c.7656T>A) is very rare (popmax 0.00446%, eas) (gnomAD).

BRCA2 p.Ile2552=

c.7656T>A · rs1002707354 · VCV2884052

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.44	GERP -4, phastCons 1
Overall
CADD	5.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,854 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000124% 2/1,613,820 alleles · very rare exomes 2/1,461,484 · genomes 0/152,336 · joint denominator

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.Ile2552=
Coding: c.7656T>A
MANE Select: NM_000059
dbSNP: rs1002707354
Type: single nucleotide variant
Location: chr13:32357780 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2552: the 'interaction with sem1' 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

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 p.Ile2552Thr Uncertain significance ★ same residue
BRCA2 p.Ile2552Val Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ile2552fs Likely pathogenic same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>A 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-ile2552 (accessed [today's date]).

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