Is CDK20 p.Glu252Val (c.755A>T) pathogenic?

CDK20 p.Glu252Val (c.755A>T) is classified Uncertain significance in CDK20 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1376); Very rare (popmax 0.00167%, amr).

How common is CDK20 p.Glu252Val (c.755A>T) in the general population?

CDK20 p.Glu252Val (c.755A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDK20 p.Glu252Val (c.755A>T)?

AlphaMissense predicts likely benign (score 0.1376) — an in-silico prediction, not a clinical call.

CDK20 p.Glu252Val

c.755A>T · rs748821346 · VCV2251770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1376 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1376	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00167% Admixed American · 1/59,980 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,780 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,980
European (non-Finnish)	0.000424%	235,982

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.Glu252Val
Coding: c.755A>T
MANE Select: NM_001039803
dbSNP: rs748821346
Type: single nucleotide variant
Location: chr9:87969282 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 252: the protein kinase domain

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

Similar variants

CDK20 p.Glu252Asp Uncertain significance ★ ⚠ same residue
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

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-glu252val (accessed [today's date]).

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