Is CDK17 p.His288Asn (c.862C>A) pathogenic?

CDK17 p.His288Asn (c.862C>A) is classified Uncertain significance in CDK17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.0808); Ultra-rare (popmax 0.0285%, nfe).

How common is CDK17 p.His288Asn (c.862C>A) in the general population?

CDK17 p.His288Asn (c.862C>A) is ultra-rare (popmax 0.0285%, nfe) (gnomAD).

What do computational predictors say about CDK17 p.His288Asn (c.862C>A)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

CDK17 p.His288Asn

c.862C>A · rs200617439 · VCV2212769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 40 kb · p 3.3e-10 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0285% European (non-Finnish) · 335/1,175,844 alleles

Filtering AF 0.026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.0215% 346/1,607,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0285%	3,510
Admixed American	0.00669%	14,947
African / African-American	0.00535%	18,689
Remaining individualsnot grpmax-eligible	0.00482%	20,759

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.His288Asn
Coding: c.862C>A
MANE Select: NM_002595
dbSNP: rs200617439
Type: single nucleotide variant
Location: chr12:96297281 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 288: 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-his288asn (accessed [today's date]).

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