Is BRCA2 p.Ser2697= (c.8091C>T) pathogenic?

BRCA2 p.Ser2697= (c.8091C>T) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 8 submitters; last evaluated 2017-06-29). Very rare (popmax 0.00267%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Ser2697= (c.8091C>T)?

BRCA2 p.Ser2697= (c.8091C>T) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ser2697= (c.8091C>T) in the general population?

BRCA2 p.Ser2697= (c.8091C>T) is very rare (popmax 0.00267%, afr) (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.Ser2697=

c.8091C>T · rs140782158 · VCV184499

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

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 -0.38	GERP -2.6
Overall
CADD	7.907	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,014 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00112% 18/1,614,078 alleles · very rare exomes 16/1,461,844 · genomes 2/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,507
East Asian	0.00223%	44,872
South Asian	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.00102%	98,334

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.Ser2697=
Coding: c.8091C>T
MANE Select: NM_000059
dbSNP: rs140782158
Type: single nucleotide variant
Location: chr13:32363293 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2697: the 'interaction with sem1' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ser2697Thr Uncertain significance ★★ same residue
BRCA2 p.Ser2697Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ser2697Arg Likely benign ★ same residue
BRCA2 p.Ser2697Ile Likely benign ★ same residue
BRCA2 p.Ser2697fs 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

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-ser2697 (accessed [today's date]).

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