Is BRCA2 p.Gln3350Ter (c.10048C>T) pathogenic?

BRCA2 p.Gln3350Ter (c.10048C>T) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-12). Absent from gnomAD v4.1; Associated with BRCA2-related disorder.

What condition is associated with BRCA2 p.Gln3350Ter (c.10048C>T)?

BRCA2 p.Gln3350Ter (c.10048C>T) is associated with BRCA2-related disorder, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Gln3350Ter (c.10048C>T) in the general population?

BRCA2 p.Gln3350Ter (c.10048C>T) is absent from gnomAD v4.1 (gnomAD).

BRCA2 p.Gln3350Ter

c.10048C>T · rs2137666093 · VCV2636400

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

BRCA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	Δ0.31	acceptor gain, 25 bp away · raw score · deltas
Pangolin	Δ0.28	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Protein: p.Gln3350Ter
Coding: c.10048C>T
MANE Select: NM_000059
dbSNP: rs2137666093
Type: single nucleotide variant
Location: chr13:32398561 (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

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 p.Gln3350Arg Uncertain significance ★★ same residue
BRCA2 p.Gln3350His Uncertain significance ★★ same residue
BRCA2 p.Gln3350Glu Uncertain significance ★ ⚠ same residue
BRCA2 p.Gln3350Leu Uncertain significance ★ same residue
BRCA2 p.Gln3350Lys Uncertain significance ★ same residue
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C 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-gln3350ter (accessed [today's date]).

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