Is CDK20 p.Lys281Arg (c.842A>G) pathogenic?

CDK20 p.Lys281Arg (c.842A>G) is classified Benign in CDK20 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-11-16). AlphaMissense: likely benign (0.0719); Low-frequency (popmax 1.24%, afr); Associated with CDK20-related disorder.

What condition is associated with CDK20 p.Lys281Arg (c.842A>G)?

CDK20 p.Lys281Arg (c.842A>G) is associated with CDK20-related disorder (ClinVar).

How common is CDK20 p.Lys281Arg (c.842A>G) in the general population?

CDK20 p.Lys281Arg (c.842A>G) is low-frequency (popmax 1.24%, afr) (gnomAD).

What do computational predictors say about CDK20 p.Lys281Arg (c.842A>G)?

AlphaMissense predicts likely benign (score 0.0719) — an in-silico prediction, not a clinical call.

CDK20 p.Lys281Arg

c.842A>G · rs28364963 · VCV3045521

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0719 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.24%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDK20-related disorder

Computational evidence

Protein change
AlphaMissense	0.0719	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.29	loss · gain 0.04 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.9	phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,981 bp · p 0.0053 · regional, not allelic
Overall
CADD	21.6	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 1.24% African / African-American · 927/74,996 alleles

Filtering AF 1.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.14%

Overall 0.064% 1,033/1,613,718 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.24%	81
Middle Eastern	0.149%	673
Admixed American	0.07%	1,428
Remaining individualsnot grpmax-eligible	0.0688%	1,453
South Asian	0.0011%	91,062
European (non-Finnish)	0.000932%	107,256

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.Lys281Arg
Coding: c.842A>G
MANE Select: NM_001039803
dbSNP: rs28364963
Type: single nucleotide variant
Location: chr9:87969195 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 281: the protein kinase domain; a UniProt-annotated variant site (in)

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

Disease context

CDK20-related disorder

Similar variants

CDK20 p.Lys281= Uncertain significance ★ same residue
CDK20 p.Lys281Glu Uncertain significance ★ ⚠ same residue
CDK20 p.Tyr215His Uncertain significance ★ ⚠ same condition
CDK20 p.Val91Met Uncertain significance ⚠ same condition
CDK20 c.190-6C>A Likely benign same condition
CDK20 c.-10C>T Likely benign same condition
CDK20 p.Ala95= Likely benign same condition
CDK20 p.Arg158Cys Likely benign same condition

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-lys281arg (accessed [today's date]).

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