Is CDK17 p.Thr393Ile (c.1178C>T) pathogenic?

CDK17 p.Thr393Ile (c.1178C>T) is classified Uncertain significance in CDK17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely pathogenic (0.9676); Very rare (popmax 0.00212%, nfe).

How common is CDK17 p.Thr393Ile (c.1178C>T) in the general population?

CDK17 p.Thr393Ile (c.1178C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about CDK17 p.Thr393Ile (c.1178C>T)?

AlphaMissense predicts likely pathogenic (score 0.9676) — an in-silico prediction, not a clinical call.

CDK17 p.Thr393Ile

c.1178C>T · VCV3489456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9676	likely pathogenic
REVEL	0.623	indeterminate
SaProt	LLR -12.32	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 3,163 bp · p 3.7e-06 · regional, not allelic
Overall
CADD	28.3	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 0.00212% European (non-Finnish) · 25/1,179,586 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,322 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,183
Remaining individualsnot grpmax-eligible	0.0016%	62,460
Finnishnot grpmax-eligible	0.00156%	63,948

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: CDK17
Protein: p.Thr393Ile
Coding: c.1178C>T
MANE Select: NM_002595
Type: single nucleotide variant
Location: chr12:96286702 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 393: the protein kinase domain

Full CDK17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK17 p.Ala439Thr Uncertain significance ★ ⚠ same type
CDK17 p.Ala86Val Uncertain significance ★ ⚠ same type
CDK17 p.Arg135Gln Uncertain significance ★ ⚠ same type
CDK17 p.Arg135Trp Uncertain significance ★ ⚠ same type
CDK17 p.Arg474Gln Uncertain significance ★ ⚠ same type
CDK17 p.Arg504Gln Uncertain significance ★ ⚠ same type
CDK17 p.Arg7Thr Uncertain significance ★ ⚠ same type
CDK17 p.Asn249Thr 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/cdk17-p-thr393ile (accessed [today's date]).

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