Is CHEK2 p.Asp347= (c.1041C>T) pathogenic?

CHEK2 p.Asp347= (c.1041C>T) is classified Likely benign in CHEK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-27). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Asp347= (c.1041C>T)?

CHEK2 p.Asp347= (c.1041C>T) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Asp347= (c.1041C>T) in the general population?

CHEK2 p.Asp347= (c.1041C>T) is absent from gnomAD v4.1 (gnomAD).

CHEK2 p.Asp347=

c.1041C>T · rs2145817317 · VCV1774229

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.77	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -3.6, phastCons 0.99
Overall
CADD	6.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHEK2
Protein: p.Asp347=
Coding: c.1041C>T
MANE Select: NM_007194
dbSNP: rs2145817317
Type: single nucleotide variant
Location: chr22:28696955 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 347: an active site; the protein kinase domain; a UniProt-annotated variant site (in)

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.Asp347Glu Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp347Gly Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp347His Uncertain significance ★★ ⚠ same residue
CHEK2 p.Asp347Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
CHEK2 p.Asp347Val Uncertain significance ★ ⚠ same residue
CHEK2 p.Asp347_Leu348insTer Pathogenic ★★ same residue
CHEK2 p.Asp347fs Pathogenic ★ same residue
CHEK2 c.1008+1G>A 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-asp347 (accessed [today's date]).

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