Is CHEK1 p.Pro172= (c.516A>G) pathogenic?

CHEK1 p.Pro172= (c.516A>G) is classified Likely benign in CHEK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). Very rare (popmax 0.00269%, afr).

How common is CHEK1 p.Pro172= (c.516A>G) in the general population?

CHEK1 p.Pro172= (c.516A>G) is very rare (popmax 0.00269%, afr) (gnomAD).

CHEK1 p.Pro172=

c.516A>G · VCV4821452

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

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 -0.43	GERP -2.4, phastCons 0.096
Overall
CADD	8.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,484 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00156% 25/1,607,532 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,242
European (non-Finnish)	0.00187%	53,561
Admixed American	0.00173%	57,864

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.Pro172=
Coding: c.516A>G
MANE Select: NM_001114122
Type: single nucleotide variant
Location: chr11:125633254 (GRCh38)
Gene constraint: LOEUF 0.831 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 168 PDB
Residue 172: the protein kinase domain; the 'interaction with clspn' region; an α-helix

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-pro172 (accessed [today's date]).

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