Is CHEK2 p.Ser31fs (c.89_90insAG) pathogenic?

CHEK2 p.Ser31fs (c.8990insAG) is classified Likely pathogenic in CHEK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-02). Absent from gnomAD; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with CHEK2 p.Ser31fs (c.89_90insAG)?

CHEK2 p.Ser31fs (c.89_90insAG) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is CHEK2 p.Ser31fs (c.89_90insAG) in the general population?

CHEK2 p.Ser31fs (c.89_90insAG) is absent from gnomAD (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.

CHEK2 p.Ser31fs

c.89_90insAG · rs2146152668 · VCV1696293

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser31fs
Coding: c.89_90insAG
MANE Select: NM_007194
dbSNP: rs2146152668
Type: Insertion
Location: chr22:28734632 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 31: the 'disordered' region

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

Disease context

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

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

CHEK2 p.Ser31Phe Uncertain significance ★★ ⚠ same residue
CHEK2 p.Ser31= Benign/Likely benign ★★ same residue
CHEK2 p.Ser31Ala Uncertain significance ★ ⚠ same residue
CHEK2 p.Ser31Cys Uncertain significance ★ ⚠ same residue
CHEK2 p.Ser31Pro Uncertain significance ★ ⚠ same residue
CHEK2 c.1009-118_1009-87delinsC Likely pathogenic ★★ same condition
CHEK2 c.1096-1G>C Likely pathogenic ★★ same condition
CHEK2 c.320-1G>T 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-ser31fs (accessed [today's date]).

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