Is CDK20 p.Ser332Leu (c.995C>T) pathogenic?

CDK20 p.Ser332Leu (c.995C>T) is classified Uncertain significance in CDK20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: likely benign (0.2688); Very rare (popmax 0.00712%, sas).

How common is CDK20 p.Ser332Leu (c.995C>T) in the general population?

CDK20 p.Ser332Leu (c.995C>T) is very rare (popmax 0.00712%, sas) (gnomAD).

What do computational predictors say about CDK20 p.Ser332Leu (c.995C>T)?

AlphaMissense predicts likely benign (score 0.2688) — an in-silico prediction, not a clinical call.

CDK20 p.Ser332Leu

c.995C>T · rs148526196 · VCV2373804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00712%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2688	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,981 bp · p 0.0053 · regional, not allelic
Overall
CADD	22.1	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 0.00712% South Asian · 6/84,230 alleles

Filtering AF 0.00305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00263% 41/1,556,082 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00712%	14,038
East Asian	0.00486%	20,577
European (non-Finnish)	0.00278%	35,929
Admixed American	0.00194%	51,516

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.Ser332Leu
Coding: c.995C>T
MANE Select: NM_001039803
dbSNP: rs148526196
Type: single nucleotide variant
Location: chr9:87967508 (GRCh38)
Gene constraint: LOEUF 1.342 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.08

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-ser332leu (accessed [today's date]).

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