Is CDK5 p.Ile10Thr (c.29T>C) pathogenic?

CDK5 p.Ile10Thr (c.29T>C) is classified Uncertain significance in CDK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely pathogenic (0.9001); Very rare (popmax 0.00223%, eas).

How common is CDK5 p.Ile10Thr (c.29T>C) in the general population?

CDK5 p.Ile10Thr (c.29T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDK5 p.Ile10Thr (c.29T>C)?

AlphaMissense predicts likely pathogenic (score 0.9001) — an in-silico prediction, not a clinical call.

CDK5 p.Ile10Thr

c.29T>C · VCV3489507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9001	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -10.97	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 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 1,256 bp · p 3.2e-10 · regional, not allelic
Overall
CADD	28.9	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 0.00223% East Asian · 1/44,864 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,611,812 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,864
African / African-American	0.00134%	74,888
European (non-Finnish)	0.000424%	235,818

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: CDK5
Protein: p.Ile10Thr
Coding: c.29T>C
MANE Select: NM_004935
Type: single nucleotide variant
Location: chr7:151057820 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 91.83 · 12 PDB
Residue 10: the protein kinase domain; a β-strand; a binding site

Full CDK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK5 p.Met230Val Uncertain significance ★★ ⚠ same type
CDK5 c.194+12G>A Benign/Likely benign ★★ same type
CDK5 c.312+3G>A Benign ★★ same type
CDK5 c.408+9T>C Likely benign ★★ same type
CDK5 c.483+11A>C Benign ★★ same type
CDK5 p.Pro240= Likely benign ★★ same type
CDK5 p.Ser72= Benign/Likely benign ★★ same type
CDK5 p.Arg50Gln Likely pathogenic ★ 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/cdk5-p-ile10thr (accessed [today's date]).

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