Is CDK18 p.Arg276Ser (c.828G>C) pathogenic?

CDK18 p.Arg276Ser (c.828G>C) is classified Uncertain significance in CDK18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: ambiguous (0.4297); Ultra-rare (popmax 0.034%, sas).

How common is CDK18 p.Arg276Ser (c.828G>C) in the general population?

CDK18 p.Arg276Ser (c.828G>C) is ultra-rare (popmax 0.034%, sas) (gnomAD).

What do computational predictors say about CDK18 p.Arg276Ser (c.828G>C)?

AlphaMissense predicts ambiguous (score 0.4297) — an in-silico prediction, not a clinical call.

CDK18 p.Arg276Ser

c.828G>C · rs145302776 · VCV2367405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4297	ambiguous
REVEL	0.084	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.022	GERP -4.9, phastCons 0.29
Regional constraint	o/e 0.97	unconstrained · MANE · 8,207 bp · p 0.52 · regional, not allelic
Overall
CADD	17.52	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 0.034% South Asian · 31/91,080 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00793% 128/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.00801%	12,488
Admixed American	0.00667%	14,998
European (non-Finnish)	0.00619%	16,165
East Asian	0.00223%	44,898
Finnishnot grpmax-eligible	0.00156%	64,030

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.Arg276Ser
Coding: c.828G>C
MANE Select: NM_212502
dbSNP: rs145302776
Type: single nucleotide variant
Location: chr1:205527892 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.28
Residue 276: 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-arg276ser (accessed [today's date]).

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