Is CDK13 p.Leu858Phe (c.2572C>T) pathogenic?

CDK13 p.Leu858Phe (c.2572C>T) is classified Conflicting classifications of pathogenicity in CDK13 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-17). AlphaMissense: likely pathogenic (0.9991); Absent from gnomAD v4.1; Associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder.

How common is CDK13 p.Leu858Phe (c.2572C>T) in the general population?

CDK13 p.Leu858Phe (c.2572C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK13 p.Leu858Phe (c.2572C>T)?

AlphaMissense predicts likely pathogenic (score 0.9991) — an in-silico prediction, not a clinical call.

CDK13 p.Leu858Phe

Q: What condition is associated with CDK13 p.Leu858Phe (c.2572C>T)?

CDK13 p.Leu858Phe (c.2572C>T) is associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (ClinVar).

Q: How is CDK13-related developmental delay-intellectual disability-facial dysmorphism-congenital heart defects syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2572C>T · VCV3897639

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital heart defects, dysmorphic facial features, and intellectual developmental disorder

Computational evidence

Protein change
AlphaMissense	0.9991	likely pathogenic · top 4% in CDK13
REVEL	0.654	pathogenic-leaning
SaProt	LLR -11.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 81 kb · p 2.9e-34 · regional, not allelic
Overall
CADD	29.4	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: CDK13
Protein: p.Leu858Phe
Coding: c.2572C>T
MANE Select: NM_003718
Type: single nucleotide variant
Location: chr7:40047849 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 858: the protein kinase domain; an α-helix

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

Disease context

congenital heart defects, dysmorphic facial features, and intellectual developmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CDK13-related developmental delay-intellectual disability-facial dysmorphism-congenital heart defects syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

CDK13 p.Leu858Val Uncertain significance ★ ⚠ same residue
CDK13 p.Ala732Thr Likely pathogenic ★★ same condition
CDK13 p.Arg737Cys Pathogenic ★★ same condition
CDK13 p.Arg751Gln Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Arg860Gln Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Arg880Cys Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Asn842Asp Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Asn842Ser Pathogenic/Likely pathogenic ★★ 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-leu858phe (accessed [today's date]).

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