Is CHEK2 p.Ser33del (c.90CTC[2]) pathogenic?

CHEK2 p.Ser33del (c.90CTC[2]) is classified Uncertain significance in CHEK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-08). Very rare (popmax 0.00223%, eas); Associated with hereditary breast carcinoma.

What condition is associated with CHEK2 p.Ser33del (c.90CTC[2])?

CHEK2 p.Ser33del (c.90CTC[2]) is associated with hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Ser33del (c.90CTC[2]) in the general population?

CHEK2 p.Ser33del (c.90CTC[2]) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

CHEK2 p.Ser33del

c.90CTC[2] · rs1569171353 · VCV1489012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.4	GERP -3

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,842 alleles

Overall 6.2e-05% 1/1,613,728 alleles · very rare exomes 1/1,461,858 · genomes 0/151,870 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHEK2
Protein: p.Ser33del
Coding: c.90CTC[2]
MANE Select: NM_007194
dbSNP: rs1569171353
Type: Microsatellite
Location: chr22:28734624 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 33: the 'disordered' region

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

Disease context

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

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

CHEK2 p.Ser33Ter Pathogenic ★★ same residue
CHEK2 p.Ser33= Benign/Likely benign ★★ same residue
CHEK2 p.Cys124fs Pathogenic ★★ same condition
CHEK2 p.Glu263fs Pathogenic ★★ same condition
CHEK2 p.Leu268fs Pathogenic ★★ same condition
CHEK2 p.Leu380fs Pathogenic ★★ same condition
CHEK2 p.Lys458fs Pathogenic ★★ same condition
CHEK2 p.Ser155fs 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-ser33del (accessed [today's date]).

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