Is CDK13 p.Ser334Arg (c.1002C>A) pathogenic?

CDK13 p.Ser334Arg (c.1002C>A) is classified Uncertain significance in CDK13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-08). AlphaMissense: likely pathogenic (0.8188); Very rare (popmax 0.00143%, nfe); Associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder.

How common is CDK13 p.Ser334Arg (c.1002C>A) in the general population?

CDK13 p.Ser334Arg (c.1002C>A) is very rare (popmax 0.00143%, nfe) (gnomAD).

What do computational predictors say about CDK13 p.Ser334Arg (c.1002C>A)?

AlphaMissense predicts likely pathogenic (score 0.8188) — an in-silico prediction, not a clinical call.

CDK13 p.Ser334Arg

Q: What condition is associated with CDK13 p.Ser334Arg (c.1002C>A)?

CDK13 p.Ser334Arg (c.1002C>A) 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.1002C>A · rs1193661434 · VCV3016292

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00143%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.8188	likely pathogenic
REVEL	0.109	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.42, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	19.3	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 0.00143% European (non-Finnish) · 16/1,117,868 alleles

Filtering AF 0.000847% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000686%

Overall 0.00122% 18/1,476,436 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00357%	28,043
European (non-Finnish)grpmax	0.00143%	69,867

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser334Arg
Coding: c.1002C>A
MANE Select: NM_003718
dbSNP: rs1193661434
Type: single nucleotide variant
Location: chr7:39951643 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 334: 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.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-ser334arg (accessed [today's date]).

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