Is CHEK2 p.Phe202fs (c.606del) pathogenic?

CHEK2 p.Phe202fs (c.606del) is classified Pathogenic/Likely pathogenic in CHEK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-06-26). Very rare (popmax 0.000345%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with CHEK2 p.Phe202fs (c.606del)?

CHEK2 p.Phe202fs (c.606del) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is CHEK2 p.Phe202fs (c.606del) in the general population?

CHEK2 p.Phe202fs (c.606del) is very rare (popmax 0.000345%, nfe) (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.Phe202fs

c.606del · rs886039609 · VCV265538

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000345%, nfe)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000345% European (non-Finnish) · 4/1,157,812 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.00028% 4/1,429,060 alleles · very rare

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.Phe202fs
Coding: c.606del
MANE Select: NM_007194
dbSNP: rs886039609
Type: Deletion
Location: chr22:28719472 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 202: a β-strand

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

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

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

Similar variants

CHEK2 p.Phe202del Uncertain significance ★ same residue
CHEK2 p.Phe202Cys Uncertain significance ★★ ⚠ same residue
CHEK2 p.Phe202Leu Uncertain significance ★★ ⚠ same residue
CHEK2 c.1096-3_1098del Likely pathogenic ★★ same condition
CHEK2 c.1375+1_1375+2del Likely pathogenic ★★ same condition
CHEK2 c.1375+1del Likely pathogenic ★★ same condition
CHEK2 c.1461+1del Likely pathogenic ★★ same condition
CHEK2 c.1462-2del 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-phe202fs (accessed [today's date]).

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