Is CDK16 p.Ser65Pro (c.193T>C) pathogenic?

CDK16 p.Ser65Pro (c.193T>C) is classified Uncertain significance in CDK16 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-12). AlphaMissense: likely benign (0.0703); Absent from gnomAD v4.1; Associated with CDK16-related disorder.

What condition is associated with CDK16 p.Ser65Pro (c.193T>C)?

CDK16 p.Ser65Pro (c.193T>C) is associated with CDK16-related disorder (ClinVar).

How common is CDK16 p.Ser65Pro (c.193T>C) in the general population?

CDK16 p.Ser65Pro (c.193T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK16 p.Ser65Pro (c.193T>C)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CDK16 p.Ser65Pro

c.193T>C · VCV3345241

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDK16-related disorder

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -4.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.44, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 954 bp · p 0.002 · regional, not allelic
Overall
CADD	21.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK16
Protein: p.Ser65Pro
Coding: c.193T>C
MANE Select: NM_006201
Type: single nucleotide variant
Location: chrX:47223750 (GRCh38)
Structure: AlphaFold pLDDT 72.92 · 3 PDB
Residue 65: a modified residue (phosphoserine); the 'disordered' region

Full CDK16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDK16-related disorder

Similar variants

CDK16 c.-6-416C>T Uncertain significance ★ same condition
CDK16 p.Asn392Ile Uncertain significance ⚠ same condition
CDK16 c.-6-431A>G Benign same condition
CDK16 p.His261Tyr Benign ⚠ same condition
CDK16 p.Leu118= Likely benign same condition
CDK16 p.Ser119= Benign same condition
CDK16 c.12+1del Uncertain significance ★ same condition
CDK16 c.1376-10C>T Benign ★★ 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/cdk16-p-ser65pro (accessed [today's date]).

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