Is CDK17 p.Pro440Ala (c.1318C>G) pathogenic?

CDK17 p.Pro440Ala (c.1318C>G) is classified Uncertain significance in CDK17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.7346); Ultra-rare (popmax 0.0103%, sas).

How common is CDK17 p.Pro440Ala (c.1318C>G) in the general population?

CDK17 p.Pro440Ala (c.1318C>G) is ultra-rare (popmax 0.0103%, sas) (gnomAD).

What do computational predictors say about CDK17 p.Pro440Ala (c.1318C>G)?

AlphaMissense predicts likely pathogenic (score 0.7346) — an in-silico prediction, not a clinical call.

CDK17 p.Pro440Ala

c.1318C>G · VCV4651522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7346 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7346	likely pathogenic
REVEL	0.347	indeterminate
SaProt	LLR -11.35	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 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,868 bp · p 0.41 · regional, not allelic
Overall
CADD	27.9	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 0.0103% South Asian · 9/87,428 alleles

Filtering AF 0.00533% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00399%

Overall 0.000655% 10/1,525,562 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0103%	9,714
Remaining individualsnot grpmax-eligible	0.00169%	59,008

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.Pro440Ala
Coding: c.1318C>G
MANE Select: NM_002595
Type: single nucleotide variant
Location: chr12:96286047 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 440: 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-pro440ala (accessed [today's date]).

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