Is BRCA2 p.Glu1940Ter (c.5818G>T) pathogenic?

BRCA2 p.Glu1940Ter (c.5818G>T) is classified Pathogenic/Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-06). Absent from gnomAD v4.1; Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Glu1940Ter (c.5818G>T)?

BRCA2 p.Glu1940Ter (c.5818G>T) is associated with BRCA2-related cancer predisposition, breast-ovarian cancer, familial, susceptibility to, 2, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Glu1940Ter (c.5818G>T) in the general population?

BRCA2 p.Glu1940Ter (c.5818G>T) is absent from gnomAD v4.1 (gnomAD).

BRCA2 p.Glu1940Ter

c.5818G>T · rs1566233278 · VCV584856

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.4, phastCons 1
Overall
CADD	34.0	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.Glu1940Ter
Coding: c.5818G>T
MANE Select: NM_000059
dbSNP: rs1566233278
Type: single nucleotide variant
Location: chr13:32340173 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1940: the 'interaction with rad51' region

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

Disease context

Also linked: breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome

Similar variants

BRCA2 p.Glu1940= Likely benign ★★ same residue
BRCA2 p.Glu1940Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Glu1940Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Glu1940Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Glu1940fs 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-glu1940ter (accessed [today's date]).

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