Is CDK16 p.Arg57Ser (c.169C>A) pathogenic?

CDK16 p.Arg57Ser (c.169C>A) is classified Uncertain significance in CDK16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1812); Absent from gnomAD v4.1.

How common is CDK16 p.Arg57Ser (c.169C>A) in the general population?

CDK16 p.Arg57Ser (c.169C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK16 p.Arg57Ser (c.169C>A)?

AlphaMissense predicts likely benign (score 0.1812) — an in-silico prediction, not a clinical call.

CDK16 p.Arg57Ser

c.169C>A · VCV4224517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1812 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1812	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.82	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 2.6	GERP -0.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 954 bp · p 0.002 · regional, not allelic
Overall
CADD	16.21	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.Arg57Ser
Coding: c.169C>A
MANE Select: NM_006201
Type: single nucleotide variant
Location: chrX:47223726 (GRCh38)
Structure: AlphaFold pLDDT 72.92 · 3 PDB
Residue 57: the 'disordered' region

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

Similar variants

CDK16 c.1376-10C>T Benign ★★ same type
CDK16 c.793-5C>T Benign ★★ same type
CDK16 c.-6-279C>T Benign ★★ same type
CDK16 p.Gly347= Likely benign ★★ same type
CDK16 p.Leu15Phe Likely pathogenic ★ ⚠ same type
CDK16 c.-5T>G Uncertain significance ★ same type
CDK16 c.-6-245C>T Uncertain significance ★ same type
CDK16 c.-6-264A>G 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/cdk16-p-arg57ser (accessed [today's date]).

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