Is CDK20 p.Arg218Cys (c.652C>T) pathogenic?

CDK20 p.Arg218Cys (c.652C>T) is classified Uncertain significance in CDK20 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.1171); Ultra-rare (popmax 0.0165%, mid).

How common is CDK20 p.Arg218Cys (c.652C>T) in the general population?

CDK20 p.Arg218Cys (c.652C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CDK20 p.Arg218Cys (c.652C>T)?

AlphaMissense predicts likely benign (score 0.1171) — an in-silico prediction, not a clinical call.

CDK20 p.Arg218Cys

c.652C>T · rs137929831 · VCV2372171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1171 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1171	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -11.25	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.22	donor loss, 35 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.6	phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,981 bp · p 0.0053 · regional, not allelic
Overall
CADD	27.2	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 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00297% 48/1,613,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
European (non-Finnish)	0.00331%	30,251
Remaining individualsnot grpmax-eligible	0.0032%	31,237
African / African-American	0.00267%	37,493
East Asian	0.00223%	44,848
Admixed American	0.00167%	59,940
Finnishnot grpmax-eligible	0.00156%	64,022
South Asian	0.0011%	91,016

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: CDK20
Protein: p.Arg218Cys
Coding: c.652C>T
MANE Select: NM_001039803
dbSNP: rs137929831
Type: single nucleotide variant
Location: chr9:87969831 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 218: the protein kinase domain

Full CDK20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK20 p.Phe204Leu Uncertain significance ★★ ⚠ same type
CDK20 c.189+23G>C Benign ★★ same type
CDK20 c.378+19C>T Benign ★★ same type
CDK20 c.564-44C>T Benign ★★ same type
CDK20 c.688-214G>A Benign ★★ same type
CDK20 c.76-20G>T Benign ★★ same type
CDK20 c.76-66T>C Benign ★★ same type
CDK20 c.*153C>T Benign ★★ 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/cdk20-p-arg218cys (accessed [today's date]).

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