Is CDK20 p.Phe323Leu (c.969C>G) pathogenic?

CDK20 p.Phe323Leu (c.969C>G) is classified Uncertain significance in CDK20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.8421); Very rare (popmax 0.00209%, nfe).

How common is CDK20 p.Phe323Leu (c.969C>G) in the general population?

CDK20 p.Phe323Leu (c.969C>G) is very rare (popmax 0.00209%, nfe) (gnomAD).

What do computational predictors say about CDK20 p.Phe323Leu (c.969C>G)?

AlphaMissense predicts likely pathogenic (score 0.8421) — an in-silico prediction, not a clinical call.

CDK20 p.Phe323Leu

c.969C>G · VCV3489478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00209%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8421	likely pathogenic
REVEL	0.14	moderately benign-leaning
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 6,981 bp · p 0.0053 · regional, not allelic
Overall
CADD	21.0	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 0.00209% European (non-Finnish) · 24/1,148,856 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00171% 24/1,402,596 alleles · very rare

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.Phe323Leu
Coding: c.969C>G
MANE Select: NM_001039803
Type: single nucleotide variant
Location: chr9:87967534 (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-phe323leu (accessed [today's date]).

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