Is CDK3 p.Val69Met (c.205G>A) pathogenic?

CDK3 p.Val69Met (c.205G>A) is classified Uncertain significance in CDK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely pathogenic (0.7632); Ultra-rare (popmax 0.025%, amr).

How common is CDK3 p.Val69Met (c.205G>A) in the general population?

CDK3 p.Val69Met (c.205G>A) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about CDK3 p.Val69Met (c.205G>A)?

AlphaMissense predicts likely pathogenic (score 0.7632) — an in-silico prediction, not a clinical call.

CDK3 p.Val69Met

c.205G>A · VCV4224558

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7632	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -12.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,994 bp · p 0.11 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.025% Admixed American · 15/59,982 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00173% 28/1,613,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
Remaining individualsnot grpmax-eligible	0.0032%	31,241
South Asian	0.0011%	91,086
European (non-Finnish)	0.000847%	118,001

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.Val69Met
Coding: c.205G>A
MANE Select: NM_001258
Type: single nucleotide variant
Location: chr17:76002032 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 2 PDB
Residue 69: the protein kinase domain; a β-strand

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-val69met (accessed [today's date]).

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