Is CDK17 p.Pro501Leu (c.1502C>T) pathogenic?

CDK17 p.Pro501Leu (c.1502C>T) is classified Uncertain significance in CDK17 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: ambiguous (0.5426); Very rare (popmax 0.00267%, afr).

How common is CDK17 p.Pro501Leu (c.1502C>T) in the general population?

CDK17 p.Pro501Leu (c.1502C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CDK17 p.Pro501Leu (c.1502C>T)?

AlphaMissense predicts ambiguous (score 0.5426) — an in-silico prediction, not a clinical call.

CDK17 p.Pro501Leu

c.1502C>T · rs201195345 · VCV3141521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.5426	ambiguous
REVEL	0.349	indeterminate
SaProt	LLR -11.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,868 bp · p 0.41 · regional, not allelic
Overall
CADD	23.6	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 0.00267% African / African-American · 2/74,862 alleles

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

Overall 0.00167% 27/1,613,656 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,431
European (non-Finnish)	0.00212%	47,196

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.Pro501Leu
Coding: c.1502C>T
MANE Select: NM_002595
dbSNP: rs201195345
Type: single nucleotide variant
Location: chr12:96280840 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 501: the 'disordered' region

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-pro501leu (accessed [today's date]).

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