Is CHEK2 p.Pro393= (c.1179T>C) pathogenic?

CHEK2 p.Pro393= (c.1179T>C) is classified Likely benign in CHEK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-15). No allele count reported in gnomAD v4.1 (AN 1,613,780); Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Pro393= (c.1179T>C)?

CHEK2 p.Pro393= (c.1179T>C) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Pro393= (c.1179T>C) in the general population?

CHEK2 p.Pro393= (c.1179T>C) is no allele count reported in gnomAD v4.1 (AN 1,613,780) (gnomAD).

CHEK2 p.Pro393=

c.1179T>C · rs2145804076 · VCV1741639

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,780)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.014	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3.4
Overall
CADD	3.426	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,780). 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.Pro393=
Coding: c.1179T>C
MANE Select: NM_007194
dbSNP: rs2145804076
Type: single nucleotide variant
Location: chr22:28695790 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 393: an α-helix; the protein kinase domain; the 't-loop/activation segment' region

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

Disease context

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

Also linked: hereditary breast carcinoma

Similar variants

CHEK2 p.Pro393Arg Uncertain significance ★★ ⚠ same residue
CHEK2 p.Pro393Leu Uncertain significance ★★ ⚠ same residue
CHEK2 p.Pro393Ser Uncertain significance ★★ ⚠ same residue
CHEK2 p.Pro393Ala Uncertain significance ★ ⚠ same residue
CHEK2 p.Pro393His Uncertain significance ★ ⚠ same residue
CHEK2 p.Pro393fs Pathogenic ★ same residue
CHEK2 p.Pro393_Val395del Uncertain significance ★ same residue
CHEK2 p.Pro393Thr Uncertain significance ★ ⚠ same residue

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-pro393 (accessed [today's date]).

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