Is CDK17 p.Ser165Arg (c.495T>A) pathogenic?

CDK17 p.Ser165Arg (c.495T>A) is classified Uncertain significance in CDK17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely pathogenic (0.9122); Very rare (popmax 8.5e-05%, nfe).

How common is CDK17 p.Ser165Arg (c.495T>A) in the general population?

CDK17 p.Ser165Arg (c.495T>A) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about CDK17 p.Ser165Arg (c.495T>A)?

AlphaMissense predicts likely pathogenic (score 0.9122) — an in-silico prediction, not a clinical call.

CDK17 p.Ser165Arg

c.495T>A · VCV3489458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9122	likely pathogenic
REVEL	0.371	indeterminate
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	GERP -4, phastCons 0.95
Regional constraint	o/e 0.68	unconstrained · MANE · 40 kb · p 3.3e-10 · regional, not allelic
Overall
CADD	18.22	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 8.5e-05% European (non-Finnish) · 1/1,176,748 alleles

Overall 6.89e-05% 1/1,450,532 alleles · very rare

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.Ser165Arg
Coding: c.495T>A
MANE Select: NM_002595
Type: single nucleotide variant
Location: chr12:96311100 (GRCh38)
Gene constraint: LOEUF 0.602 · pLI 0.83 (gnomAD)
Structure: AlphaFold pLDDT 70.51
Residue 165: a modified residue (phosphoserine)

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-ser165arg (accessed [today's date]).

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