Is BRCA2 p.Ser2148= (c.6444T>C) pathogenic?

BRCA2 p.Ser2148= (c.6444T>C) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 8 submitters; last evaluated 2017-06-29). Ultra-rare (popmax 0.0169%, mid); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Ser2148= (c.6444T>C)?

BRCA2 p.Ser2148= (c.6444T>C) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ser2148= (c.6444T>C) in the general population?

BRCA2 p.Ser2148= (c.6444T>C) is ultra-rare (popmax 0.0169%, mid) (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.Ser2148=

c.6444T>C · rs771131099 · VCV415692

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

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 -0.11	GERP -2.1
Overall
CADD	1.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,928 alleles

Filtering AF 0.00797% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00622%

Overall 0.00188% 30/1,592,250 alleles · ultra-rare exomes 30/1,439,916 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,928
South Asian	0.0139%	7,211
Remaining individualsnot grpmax-eligible	0.00163%	61,430
European (non-Finnish)	0.00136%	73,326

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.Ser2148=
Coding: c.6444T>C
MANE Select: NM_000059
dbSNP: rs771131099
Type: single nucleotide variant
Location: chr13:32340799 (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

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.Ser2148Ala Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2148Cys Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2148Phe Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2148Tyr Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2148Pro Likely benign ★ same residue
BRCA2 p.Ser2148_Ile2149insTer Pathogenic ★★★ same residue
BRCA2 p.Ser2148fs Pathogenic ★★★ same residue
BRCA2 c.316+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-ser2148 (accessed [today's date]).

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