Is CDK15 p.Pro342Leu (c.1025C>T) pathogenic?

CDK15 p.Pro342Leu (c.1025C>T) is classified Uncertain significance in CDK15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.0801); Ultra-rare (popmax 0.0825%, mid).

How common is CDK15 p.Pro342Leu (c.1025C>T) in the general population?

CDK15 p.Pro342Leu (c.1025C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about CDK15 p.Pro342Leu (c.1025C>T)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

CDK15 p.Pro342Leu

c.1025C>T · VCV3265434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.19	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 0.85	GERP -1.1, phastCons 0.006
Regional constraint	o/e 1.03	unconstrained · MANE · 84 kb · p 0.56 · regional, not allelic
Overall
CADD	10.62	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

Grpmax group 0.0825% Middle Eastern · 5/6,060 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.000682% 11/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
African / African-American	0.00533%	18,756
Remaining individualsnot grpmax-eligible	0.0016%	62,502
South Asian	0.0011%	91,070

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: CDK15
Protein: p.Pro342Leu
Coding: c.1025C>T
MANE Select: NM_001366386
Type: single nucleotide variant
Location: chr2:201872293 (GRCh38)
Gene constraint: LOEUF 1.291 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.75
Residue 342: the protein kinase domain

Full CDK15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK15 p.Ala115Val Uncertain significance ★ ⚠ same type
CDK15 p.Ala378Thr Uncertain significance ★ ⚠ same type
CDK15 p.Ala63Ser Uncertain significance ★ ⚠ same type
CDK15 p.Arg148Gln Uncertain significance ★ ⚠ same type
CDK15 p.Arg247Gln Uncertain significance ★ ⚠ same type
CDK15 p.Arg266Trp Uncertain significance ★ ⚠ same type
CDK15 p.Arg74Gln Uncertain significance ★ ⚠ same type
CDK15 p.Asn105Tyr 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/cdk15-p-pro342leu (accessed [today's date]).

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