Is CDK16 p.Leu15Phe (c.43C>T) pathogenic?

CDK16 p.Leu15Phe (c.43C>T) is classified Likely pathogenic in CDK16 (ClinVar, Single submitter, 1 submitter). AlphaMissense: ambiguous (0.4752); Absent from gnomAD v4.1; Associated with oligospermia.

What condition is associated with CDK16 p.Leu15Phe (c.43C>T)?

CDK16 p.Leu15Phe (c.43C>T) is associated with oligospermia (ClinVar).

How common is CDK16 p.Leu15Phe (c.43C>T) in the general population?

CDK16 p.Leu15Phe (c.43C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK16 p.Leu15Phe (c.43C>T)?

AlphaMissense predicts ambiguous (score 0.4752) — an in-silico prediction, not a clinical call.

CDK16 p.Leu15Phe

c.43C>T · VCV3239639

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

oligospermia

Computational evidence

Protein change
AlphaMissense	0.4752	ambiguous
REVEL	0.227	benign-leaning
SaProt	LLR -6.32	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 954 bp · p 0.002 · regional, not allelic
Overall
CADD	25.3	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

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.Leu15Phe
Coding: c.43C>T
MANE Select: NM_006201
Type: single nucleotide variant
Location: chrX:47223600 (GRCh38)
Structure: AlphaFold pLDDT 72.92 · 3 PDB
Residue 15: 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.Arg16Gln Uncertain significance ★ ⚠ 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-leu15phe (accessed [today's date]).

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