Is CDK16 p.Arg16Gln (c.47G>A) pathogenic?

CDK16 p.Arg16Gln (c.47G>A) is classified Uncertain significance in CDK16 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.7365); Ultra-rare (popmax 0.0178%, eas); Associated with oligospermia.

What condition is associated with CDK16 p.Arg16Gln (c.47G>A)?

CDK16 p.Arg16Gln (c.47G>A) is associated with oligospermia (ClinVar).

How common is CDK16 p.Arg16Gln (c.47G>A) in the general population?

CDK16 p.Arg16Gln (c.47G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CDK16 p.Arg16Gln (c.47G>A)?

AlphaMissense predicts likely pathogenic (score 0.7365) — an in-silico prediction, not a clinical call.

CDK16 p.Arg16Gln

c.47G>A · VCV3239640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7365 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oligospermia

Computational evidence

Protein change
AlphaMissense	0.7365	likely pathogenic
REVEL	0.259	benign-leaning
SaProt	LLR -7.47	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 954 bp · p 0.002 · regional, not allelic
Overall
CADD	23.3	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 0.0178% East Asian · 6/33,733 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00527%

Overall 0.00141% 17/1,209,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,622
South Asian	0.00528%	18,939
Admixed American	0.00436%	22,918
European (non-Finnish)	0.00067%	149,148

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: CDK16
Protein: p.Arg16Gln
Coding: c.47G>A
MANE Select: NM_006201
Type: single nucleotide variant
Location: chrX:47223604 (GRCh38)
Structure: AlphaFold pLDDT 72.92 · 3 PDB
Residue 16: the 'disordered' region

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

Disease context

oligospermia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK16 p.Leu15Phe Likely pathogenic ★ ⚠ same condition
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 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-arg16gln (accessed [today's date]).

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