Is CDK13 p.Ser662del (c.1984_1986del) pathogenic?

CDK13 p.Ser662del (c.19841986del) is classified Uncertain significance in CDK13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-13). Ultra-rare (popmax 0.0165%, mid); Associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder.

How common is CDK13 p.Ser662del (c.1984_1986del) in the general population?

CDK13 p.Ser662del (c.1984_1986del) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CDK13 p.Ser662del

Q: What condition is associated with CDK13 p.Ser662del (c.1984_1986del)?

CDK13 p.Ser662del (c.1984_1986del) 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.1984_1986del · rs1281631847 · VCV1973726

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP -3.1, phastCons 0.95

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
European (non-Finnish)	0.000339%	294,948

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.Ser662del
Coding: c.1984_1986del
MANE Select: NM_003718
dbSNP: rs1281631847
Type: Deletion
Location: chr7:39997606 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 662: the 'disordered' region

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.Leu61fs Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Arg110fs Likely pathogenic ★ same condition
CDK13 p.Glu775fs Likely pathogenic ★ same condition
CDK13 p.Phe809fs Likely pathogenic ★ same condition
CDK13 p.Ala633del Uncertain significance ★ same condition
CDK13 p.Glu195_Arg200del Uncertain significance ★ same condition
CDK13 p.Glu769_Ile770insTer Uncertain significance ★ same condition
CDK13 p.Ser662= Likely benign ★ same residue

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-ser662del (accessed [today's date]).

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