Is CDK18 p.Glu190Asp (c.570G>C) pathogenic?

CDK18 p.Glu190Asp (c.570G>C) is classified Uncertain significance in CDK18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is CDK18 p.Glu190Asp (c.570G>C) in the general population?

CDK18 p.Glu190Asp (c.570G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK18 p.Glu190Asp (c.570G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

CDK18 p.Glu190Asp

c.570G>C · VCV4651531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 3% in CDK18
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -11.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -3.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,207 bp · p 0.52 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: CDK18
Protein: p.Glu190Asp
Coding: c.570G>C
MANE Select: NM_212502
Type: single nucleotide variant
Location: chr1:205526178 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.28
Residue 190: the protein kinase domain

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

Similar variants

CDK18 p.Glu190Gln Uncertain significance ★ ⚠ same residue
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

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-glu190asp (accessed [today's date]).

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