Is CDK3 p.Ala282Asp (c.845C>A) pathogenic?

CDK3 p.Ala282Asp (c.845C>A) is classified Uncertain significance in CDK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.1494); Ultra-rare (popmax 0.0178%, eas).

How common is CDK3 p.Ala282Asp (c.845C>A) in the general population?

CDK3 p.Ala282Asp (c.845C>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CDK3 p.Ala282Asp (c.845C>A)?

AlphaMissense predicts likely benign (score 0.1494) — an in-silico prediction, not a clinical call.

CDK3 p.Ala282Asp

c.845C>A · VCV3489486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1494 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1494	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -7.42	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 1.2	GERP -3.1, phastCons 0.028
Regional constraint	o/e 0.92	unconstrained · MANE · 3,994 bp · p 0.11 · regional, not allelic
Overall
CADD	13.47	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 0.0178% East Asian · 8/44,872 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00118% 19/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,609
Remaining individualsnot grpmax-eligible	0.008%	12,500
South Asian	0.00659%	15,181

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.Ala282Asp
Coding: c.845C>A
MANE Select: NM_001258
Type: single nucleotide variant
Location: chr17:76005350 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 2 PDB
Residue 282: 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.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
CDK3 p.Arg296Cys 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-ala282asp (accessed [today's date]).

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