Is CDK18 p.Pro384Arg (c.1151C>G) pathogenic?

CDK18 p.Pro384Arg (c.1151C>G) is classified Uncertain significance in CDK18 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.1376); Very rare (popmax 8.47e-05%, nfe).

How common is CDK18 p.Pro384Arg (c.1151C>G) in the general population?

CDK18 p.Pro384Arg (c.1151C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CDK18 p.Pro384Arg (c.1151C>G)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

CDK18 p.Pro384Arg

c.1151C>G · rs756053212 · VCV2323686

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -11.49	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,207 bp · p 0.52 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,954 alleles

Overall 6.2e-05% 1/1,613,904 alleles · very rare exomes 0/1,461,658 · genomes 1/152,246 · joint denominator

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.Pro384Arg
Coding: c.1151C>G
MANE Select: NM_212502
dbSNP: rs756053212
Type: single nucleotide variant
Location: chr1:205529402 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.28
Residue 384: 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-pro384arg (accessed [today's date]).

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