Is CDK13 p.Thr1445Met (c.4334C>T) pathogenic?

CDK13 p.Thr1445Met (c.4334C>T) is classified Likely benign in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-05). AlphaMissense: likely benign (0.0797); Ultra-rare (popmax 0.0364%, sas); Associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder.

How common is CDK13 p.Thr1445Met (c.4334C>T) in the general population?

CDK13 p.Thr1445Met (c.4334C>T) is ultra-rare (popmax 0.0364%, sas) (gnomAD).

What do computational predictors say about CDK13 p.Thr1445Met (c.4334C>T)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

CDK13 p.Thr1445Met

Q: What condition is associated with CDK13 p.Thr1445Met (c.4334C>T)?

CDK13 p.Thr1445Met (c.4334C>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.4334C>T · rs755651415 · VCV2690476

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0364%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.94	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 6	GERP 1.9, phastCons 0.82
Regional constraint	o/e 0.82	unconstrained · MANE · 6,791 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.0364% South Asian · 33/90,594 alleles

Filtering AF 0.0266% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0233%

Overall 0.00304% 49/1,611,468 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0364%	2,745
Remaining individualsnot grpmax-eligible	0.0016%	62,372
European (non-Finnish)	0.00127%	78,584

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.Thr1445Met
Coding: c.4334C>T
MANE Select: NM_003718
dbSNP: rs755651415
Type: single nucleotide variant
Location: chr7:40094775 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB

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.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
CDK13 p.Asp855Asn 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-thr1445met (accessed [today's date]).

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