Is CDK18 p.Arg19Cys (c.55C>T) pathogenic?

CDK18 p.Arg19Cys (c.55C>T) is classified Uncertain significance in CDK18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: ambiguous (0.3941); Very rare (popmax 0.00891%, eas).

How common is CDK18 p.Arg19Cys (c.55C>T) in the general population?

CDK18 p.Arg19Cys (c.55C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CDK18 p.Arg19Cys (c.55C>T)?

AlphaMissense predicts ambiguous (score 0.3941) — an in-silico prediction, not a clinical call.

CDK18 p.Arg19Cys

c.55C>T · rs760625150 · VCV2596265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3941	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -8.10	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,207 bp · p 0.52 · regional, not allelic
Overall
CADD	32.0	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 0.00891% East Asian · 4/44,892 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00155% 25/1,613,540 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.00144%	69,387
African / African-American	0.00134%	74,894
South Asian	0.0011%	91,084

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.Arg19Cys
Coding: c.55C>T
MANE Select: NM_212502
dbSNP: rs760625150
Type: single nucleotide variant
Location: chr1:205523222 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.28

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

Similar variants

CDK18 p.Arg19Gly 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-arg19cys (accessed [today's date]).

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