Is CDK3 p.Glu98Ala (c.293A>C) pathogenic?

CDK3 p.Glu98Ala (c.293A>C) is classified Uncertain significance in CDK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.1007); Very rare (popmax 8.47e-05%, nfe).

How common is CDK3 p.Glu98Ala (c.293A>C) in the general population?

CDK3 p.Glu98Ala (c.293A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CDK3 p.Glu98Ala (c.293A>C)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

CDK3 p.Glu98Ala

c.293A>C · VCV4224562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -2.99	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 3.2	GERP -3.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,994 bp · p 0.11 · regional, not allelic
Overall
CADD	11.82	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 8.47e-05% European (non-Finnish) · 1/1,179,956 alleles

Overall 0.000659% 1/151,776 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: CDK3
Protein: p.Glu98Ala
Coding: c.293A>C
MANE Select: NM_001258
Type: single nucleotide variant
Location: chr17:76002120 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 2 PDB
Residue 98: the protein kinase domain

Full CDK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK3 p.Ala170Ser Uncertain significance ★ ⚠ same type
CDK3 p.Ala282Asp Uncertain significance ★ ⚠ same type
CDK3 p.Arg126Gln Uncertain significance ★ ⚠ same type
CDK3 p.Arg150Cys Uncertain significance ★ ⚠ same type
CDK3 p.Arg150His Uncertain significance ★ ⚠ same type
CDK3 p.Arg199Gln Uncertain significance ★ ⚠ same type
CDK3 p.Arg214Cys Uncertain significance ★ ⚠ same type
CDK3 p.Arg217His Uncertain significance ★ ⚠ 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/cdk3-p-glu98ala (accessed [today's date]).

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