Is CHEK1 p.Val339= (c.1017A>G) pathogenic?

CHEK1 p.Val339= (c.1017A>G) is classified Likely benign in CHEK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-28). Very rare (popmax 0.0022%, sas).

How common is CHEK1 p.Val339= (c.1017A>G) in the general population?

CHEK1 p.Val339= (c.1017A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

CHEK1 p.Val339=

c.1017A>G · rs754935840 · VCV1747016

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 0.68	GERP -3.5, phastCons 0.94
Overall
CADD	5.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,872 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: CHEK1
Protein: p.Val339=
Coding: c.1017A>G
MANE Select: NM_001114122
dbSNP: rs754935840
Type: single nucleotide variant
Location: chr11:125644184 (GRCh38)
Gene constraint: LOEUF 0.831 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 168 PDB

Full CHEK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHEK1 p.Gln346Ter Likely pathogenic ★★ same type
CHEK1 p.Arg277Gln Uncertain significance ★★ ⚠ same type
CHEK1 p.Arg420= Benign ★★ same type
CHEK1 p.Ile471Val Benign ★★ same type
CHEK1 c.-160C>T Uncertain significance ★ same type
CHEK1 c.-83T>C Uncertain significance ★ same type
CHEK1 p.Ala200Ser Uncertain significance ★ ⚠ same type
CHEK1 p.Ala34Pro Uncertain significance ★ ⚠ same type

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/chek1-p-val339 (accessed [today's date]).

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