Is CHEK2 p.Asp293Ter (c.876dup) pathogenic?

CHEK2 p.Asp293Ter (c.876dup) is classified Pathogenic in CHEK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-17). No allele count reported in gnomAD v4.1 (AN 1,555,868); Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Asp293Ter (c.876dup)?

CHEK2 p.Asp293Ter (c.876dup) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Asp293Ter (c.876dup) in the general population?

CHEK2 p.Asp293Ter (c.876dup) is no allele count reported in gnomAD v4.1 (AN 1,555,868) (gnomAD).

CHEK2 p.Asp293Ter

c.876dup · rs772683219 · VCV234121

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,555,868)

Conditions

hereditary neoplastic syndrome

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 8 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,555,868). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHEK2
Protein: p.Asp293Ter
Coding: c.876dup
MANE Select: NM_007194
dbSNP: rs772683219
Type: Duplication
Location: chr22:28703536 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 293: a β-strand; the protein kinase domain

Full CHEK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast carcinoma

Similar variants

CHEK2 p.Asp293fs Pathogenic ★★ same residue
CHEK2 p.Asp293Ala Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp293Asn Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp293Gly Uncertain significance ★★ same residue
CHEK2 p.Asp293= Benign/Likely benign ★★ same residue
CHEK2 p.Asp293His Uncertain significance ★ same residue
CHEK2 p.Asp293Val Uncertain significance ★ ⚠ same residue
CHEK2 p.Arg431Ter Pathogenic/Likely 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/chek2-p-asp293ter (accessed [today's date]).

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