Is CDK13 p.Pro414Leu (c.1241C>T) pathogenic?

CDK13 p.Pro414Leu (c.1241C>T) is classified Uncertain significance in CDK13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-20). AlphaMissense: likely pathogenic (0.9345); Very rare (popmax 0.00113%, sas); Associated with Inborn genetic diseases.

What condition is associated with CDK13 p.Pro414Leu (c.1241C>T)?

CDK13 p.Pro414Leu (c.1241C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK13 p.Pro414Leu (c.1241C>T) in the general population?

CDK13 p.Pro414Leu (c.1241C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

What do computational predictors say about CDK13 p.Pro414Leu (c.1241C>T)?

AlphaMissense predicts likely pathogenic (score 0.9345) — an in-silico prediction, not a clinical call.

CDK13 p.Pro414Leu

c.1241C>T · rs781568114 · VCV2874386

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9345 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9345	likely pathogenic
REVEL	0.344	indeterminate
SaProt	LLR -10.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00113% South Asian · 1/88,508 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000561% 9/1,603,610 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00113%	88,508
European (non-Finnish)	0.00068%	147,161

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: CDK13
Protein: p.Pro414Leu
Coding: c.1241C>T
MANE Select: NM_003718
dbSNP: rs781568114
Type: single nucleotide variant
Location: chr7:39987628 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 414: the 'disordered' region

Full CDK13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK13 p.Pro414= Likely benign ★★ same residue
CDK13 p.Ala1301Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala134Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala182Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala331Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala504Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala970Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Arg1366Cys Uncertain significance ★★ ⚠ same condition

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/cdk13-p-pro414leu (accessed [today's date]).

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