Is CHEK2 p.Val200= (c.600C>G) pathogenic?

CHEK2 p.Val200= (c.600C>G) is classified Benign/Likely benign in CHEK2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-02). Ultra-rare (popmax 0.017%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with CHEK2 p.Val200= (c.600C>G)?

CHEK2 p.Val200= (c.600C>G) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CHEK2 p.Val200= (c.600C>G) in the general population?

CHEK2 p.Val200= (c.600C>G) is ultra-rare (popmax 0.017%, mid) (gnomAD).

CHEK2 p.Val200=

c.600C>G · rs141685349 · VCV186108

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -2.6, phastCons 0.005
Overall
CADD	3.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% Middle Eastern · 1/5,876 alleles

Filtering AF 0.00236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00285% 45/1,578,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,876
Finnishnot grpmax-eligible	0.00963%	10,383
European (non-Finnish)	0.0032%	31,223
Remaining individualsnot grpmax-eligible	0.00164%	61,046

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.Val200=
Coding: c.600C>G
MANE Select: NM_007194
dbSNP: rs141685349
Type: single nucleotide variant
Location: chr22:28719478 (GRCh38)
Gene constraint: LOEUF 1.399 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 38 PDB
Residue 200: a β-strand

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.Val200Ile Uncertain significance ★★ ⚠ same residue
CHEK2 p.Val200Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CHEK2 p.Val200Asp Uncertain significance ★ ⚠ same residue
CHEK2 p.Val200Phe Uncertain significance ★ ⚠ same residue
CHEK2 c.1008+1G>A Likely pathogenic ★★ same condition
CHEK2 c.1008+1G>T Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>A Likely pathogenic ★★ same condition
CHEK2 c.1008+2T>G 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-val200 (accessed [today's date]).

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