Is CHEK2 p.Ile286= (c.858C>T) pathogenic?

CHEK2 p.Ile286= (c.858C>T) is classified Likely benign in CHEK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-20). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with CHEK2 p.Ile286= (c.858C>T)?

CHEK2 p.Ile286= (c.858C>T) is associated with hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Ile286= (c.858C>T) in the general population?

CHEK2 p.Ile286= (c.858C>T) is absent from gnomAD v4.1 (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.Ile286=

c.858C>T · rs2145878513 · VCV1081687

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,559,322)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.242	benign-leaning
Splicing
SpliceAI	Δ0.48	acceptor loss · deltas
Pangolin	Δ0.38	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Overall
CADD	5.425	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,559,322). 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.Ile286=
Coding: c.858C>T
MANE Select: NM_007194
dbSNP: rs2145878513
Type: single nucleotide variant
Location: chr22:28703555 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 286: the protein kinase domain

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.Ile286Phe Uncertain significance ★★ ⚠ same residue
CHEK2 p.Ile286Thr Uncertain significance ★★ ⚠ same residue
CHEK2 p.Ile286Val Uncertain significance ★★ ⚠ same residue
CHEK2 p.Ile286Leu Uncertain significance ★ ⚠ same residue
CHEK2 p.Ile286del Uncertain significance ★ same residue
CHEK2 p.Ile286Met Uncertain significance ★ same residue
CHEK2 c.1008+1G>A Likely pathogenic ★★ same condition
CHEK2 c.1008+1G>T 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-ile286 (accessed [today's date]).

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