Is CDK18 p.Leu253= (c.759C>T) pathogenic?

CDK18 p.Leu253= (c.759C>T) is classified Likely benign in CDK18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). Ultra-rare (popmax 0.0756%, nfe).

How common is CDK18 p.Leu253= (c.759C>T) in the general population?

CDK18 p.Leu253= (c.759C>T) is ultra-rare (popmax 0.0756%, nfe) (gnomAD).

CDK18 p.Leu253=

c.759C>T · rs139419406 · VCV2639854

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0756%, nfe)

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 -8	GERP -4.9
Overall
CADD	2.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0756% European (non-Finnish) · 892/1,179,902 alleles

Filtering AF 0.0714% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0698%

Overall 0.0644% 1,039/1,613,832 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0896%	1,116
European (non-Finnish)grpmax	0.0756%	1,323
East Asian	0.0579%	1,727
South Asian	0.0417%	2,397
Admixed American	0.0317%	3,157
Middle Eastern	0.0164%	6,084
African / African-American	0.00668%	14,978
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Finnishnot grpmax-eligible	0.00156%	64,024

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CDK18
Protein: p.Leu253=
Coding: c.759C>T
MANE Select: NM_212502
dbSNP: rs139419406
Type: single nucleotide variant
Location: chr1:205527823 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.28
Residue 253: the protein kinase domain

Full CDK18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK18 c.273+26G>A Uncertain significance ★★ same type
CDK18 p.Arg162Cys Uncertain significance ★★ ⚠ same type
CDK18 c.273+41G>A Uncertain significance ★ same type
CDK18 c.273+44C>T Uncertain significance ★ same type
CDK18 c.273+47A>C Uncertain significance ★ same type
CDK18 c.273+4A>T Uncertain significance ★ same type
CDK18 c.273+62G>C Uncertain significance ★ same type
CDK18 c.273+82C>A 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/cdk18-p-leu253 (accessed [today's date]).

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