Is CDK3 p.Val154Met (c.460G>A) pathogenic?

CDK3 p.Val154Met (c.460G>A) is classified Uncertain significance in CDK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: ambiguous (0.3787); Ultra-rare (popmax 0.066%, mid).

How common is CDK3 p.Val154Met (c.460G>A) in the general population?

CDK3 p.Val154Met (c.460G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about CDK3 p.Val154Met (c.460G>A)?

AlphaMissense predicts ambiguous (score 0.3787) — an in-silico prediction, not a clinical call.

CDK3 p.Val154Met

c.460G>A · rs145748425 · VCV2293680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Computational evidence

Protein change
AlphaMissense	0.3787	ambiguous
REVEL	0.338	indeterminate
SaProt	LLR -11.62	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,994 bp · p 0.11 · regional, not allelic
Overall
CADD	22.4	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 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.0314% 507/1,612,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.449%	223
Middle Easterngrpmax	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0432%	2,314
European (non-Finnish)	0.0276%	3,619
South Asian	0.011%	9,105
Admixed American	0.005%	19,995
African / African-American	0.004%	25,001
Finnishnot grpmax-eligible	0.0016%	62,556

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val154Met
Coding: c.460G>A
MANE Select: NM_001258
dbSNP: rs145748425
Type: single nucleotide variant
Location: chr17:76002392 (GRCh38)
Gene constraint: LOEUF 1.082 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.31 · 2 PDB
Residue 154: 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-val154met (accessed [today's date]).

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