Is CHEK2 p.Ser40Pro (c.118_119delinsCC) pathogenic?

CHEK2 p.Ser40Pro (c.118119delinsCC) is classified Uncertain significance in CHEK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with CHEK2 p.Ser40Pro (c.118_119delinsCC)?

CHEK2 p.Ser40Pro (c.118_119delinsCC) is associated with hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Ser40Pro (c.118_119delinsCC) in the general population?

CHEK2 p.Ser40Pro (c.118_119delinsCC) is absent from gnomAD (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.Ser40Pro

c.118_119delinsCC · rs1569171216 · VCV572199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3.7	GERP 0.58, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 47 kb · p 0.57 · regional, not allelic

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.Ser40Pro
Coding: c.118_119delinsCC
MANE Select: NM_007194
dbSNP: rs1569171216
Type: Indel
Location: chr22:28734603 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 40: 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.Ser40Gly Uncertain significance ★★ ⚠ same residue
CHEK2 p.Ser40= Benign/Likely benign ★★ same residue
CHEK2 p.Ser40fs Pathogenic ★ same residue
CHEK2 p.Ser40Asn Uncertain significance ★ ⚠ same residue
CHEK2 p.Ser40Thr Uncertain significance ★ ⚠ same residue
CHEK2 c.1009-118_1009-87delinsC Likely pathogenic ★★ same condition
CHEK2 c.847-14_847-2delinsGG Likely pathogenic ★★ same condition
CHEK2 c.908+1_908+13delinsTTTAAAA 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-ser40pro (accessed [today's date]).

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