Is CDK13 p.Pro297Ser (c.889C>T) pathogenic?

CDK13 p.Pro297Ser (c.889C>T) is classified Uncertain significance in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.5458); Very rare (popmax 0.00035%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDK13 p.Pro297Ser (c.889C>T)?

CDK13 p.Pro297Ser (c.889C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK13 p.Pro297Ser (c.889C>T) in the general population?

CDK13 p.Pro297Ser (c.889C>T) is very rare (popmax 0.00035%, nfe) (gnomAD).

What do computational predictors say about CDK13 p.Pro297Ser (c.889C>T)?

AlphaMissense predicts ambiguous (score 0.5458) — an in-silico prediction, not a clinical call.

CDK13 p.Pro297Ser

c.889C>T · VCV4224473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00035%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5458	ambiguous
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	24.6	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 0.00035% European (non-Finnish) · 4/1,143,756 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.00026% 4/1,536,556 alleles · very rare exomes 4/1,384,230 · genomes 0/152,326 · joint denominator

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.Pro297Ser
Coding: c.889C>T
MANE Select: NM_003718
Type: single nucleotide variant
Location: chr7:39951530 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 297: 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.Pro297= Benign/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-pro297ser (accessed [today's date]).

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