Is CDK18 p.Thr336Arg (c.1007C>G) pathogenic?

CDK18 p.Thr336Arg (c.1007C>G) is classified Uncertain significance in CDK18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely pathogenic (0.67); Ultra-rare (popmax 0.0181%, eas).

How common is CDK18 p.Thr336Arg (c.1007C>G) in the general population?

CDK18 p.Thr336Arg (c.1007C>G) is ultra-rare (popmax 0.0181%, eas) (gnomAD).

What do computational predictors say about CDK18 p.Thr336Arg (c.1007C>G)?

AlphaMissense predicts likely pathogenic (score 0.67) — an in-silico prediction, not a clinical call.

CDK18 p.Thr336Arg

c.1007C>G · VCV3999610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.67 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.67	likely pathogenic
REVEL	0.385	indeterminate
SaProt	LLR -11.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,207 bp · p 0.52 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.0181% East Asian · 8/44,182 alleles

Filtering AF 0.00895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0065%

Overall 0.00094% 15/1,596,426 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0181%	5,523
Remaining individualsnot grpmax-eligible	0.00971%	10,301
South Asian	0.00114%	87,726

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.Thr336Arg
Coding: c.1007C>G
MANE Select: NM_212502
Type: single nucleotide variant
Location: chr1:205529031 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.28
Residue 336: 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-thr336arg (accessed [today's date]).

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