Is CDK15 p.Val142Leu (c.424G>C) pathogenic?

CDK15 p.Val142Leu (c.424G>C) is classified Uncertain significance in CDK15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: ambiguous (0.4164); Very rare (popmax 8.48e-05%, nfe).

How common is CDK15 p.Val142Leu (c.424G>C) in the general population?

CDK15 p.Val142Leu (c.424G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDK15 p.Val142Leu (c.424G>C)?

AlphaMissense predicts ambiguous (score 0.4164) — an in-silico prediction, not a clinical call.

CDK15 p.Val142Leu

c.424G>C · VCV3489447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4164	ambiguous
REVEL	0.26	benign-leaning
SaProt	LLR -8.63	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 8.5	GERP 0.98, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 84 kb · p 0.56 · regional, not allelic
Overall
CADD	22.3	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 8.48e-05% European (non-Finnish) · 1/1,179,276 alleles

Overall 6.85e-05% 1/1,460,740 alleles · very rare

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.Val142Leu
Coding: c.424G>C
MANE Select: NM_001366386
Type: single nucleotide variant
Location: chr2:201812538 (GRCh38)
Gene constraint: LOEUF 1.291 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.75
Residue 142: the protein kinase domain

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

Similar variants

CDK15 p.Val142Ile Uncertain significance ★ ⚠ same residue
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

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-val142leu (accessed [today's date]).

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