Is BRCA2 p.Thr867= (c.2601T>G) pathogenic?

BRCA2 p.Thr867= (c.2601T>G) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 8 submitters; last evaluated 2017-06-29). Very rare (popmax 0.00237%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Thr867= (c.2601T>G)?

BRCA2 p.Thr867= (c.2601T>G) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Thr867= (c.2601T>G) in the general population?

BRCA2 p.Thr867= (c.2601T>G) is very rare (popmax 0.00237%, sas) (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.Thr867=

c.2601T>G · rs730881589 · VCV182285

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00237%, sas)

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 -1	GERP -4.9
Overall
CADD	3.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% South Asian · 2/84,474 alleles

Filtering AF 0.000393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000147%

Overall 0.000505% 8/1,584,236 alleles · very rare exomes 7/1,432,138 · genomes 1/152,098 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00237%	42,237
Admixed American	0.00198%	50,626
Remaining individualsnot grpmax-eligible	0.00164%	61,142
European (non-Finnish)	0.000341%	293,095

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.Thr867=
Coding: c.2601T>G
MANE Select: NM_000059
dbSNP: rs730881589
Type: single nucleotide variant
Location: chr13:32336956 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 867: the 'interaction with npm1' 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.Thr867Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Thr867Ser Conflicting classifications of pathogenicity ★ ⚠ 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
BRCA2 c.475+1G>T 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-thr867 (accessed [today's date]).

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