Is CHEK2 p.Trp97Ter (c.290G>A) pathogenic?

CHEK2 p.Trp97Ter (c.290G>A) is classified Pathogenic in CHEK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-07). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Trp97Ter (c.290G>A)?

CHEK2 p.Trp97Ter (c.290G>A) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Trp97Ter (c.290G>A) in the general population?

CHEK2 p.Trp97Ter (c.290G>A) is absent from gnomAD v4.1 (gnomAD).

CHEK2 p.Trp97Ter

c.290G>A · rs2146144384 · VCV2584140

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2 of 15
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Overall
CADD	38.0	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: CHEK2
Protein: p.Trp97Ter
Coding: c.290G>A
MANE Select: NM_007194
dbSNP: rs2146144384
Type: single nucleotide variant
Location: chr22:28734432 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 97: a β-strand

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.Trp97Arg Uncertain significance ★★ ⚠ same residue
CHEK2 p.Trp97fs Pathogenic ★ same residue
CHEK2 c.1008+1G>A Likely pathogenic ★★ same condition
CHEK2 c.1008+1G>T Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>A Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>G Likely pathogenic ★★ same condition
CHEK2 c.1009-1G>A Likely pathogenic ★★ same condition
CHEK2 c.1009-2A>C 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-trp97ter (accessed [today's date]).

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