Is CDK13 p.Tyr362Cys (c.1085A>G) pathogenic?

CDK13 p.Tyr362Cys (c.1085A>G) is classified Uncertain significance in CDK13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-24). AlphaMissense: likely benign (0.3052); Very rare (popmax 0.00592%, afr); Associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder.

How common is CDK13 p.Tyr362Cys (c.1085A>G) in the general population?

CDK13 p.Tyr362Cys (c.1085A>G) is very rare (popmax 0.00592%, afr) (gnomAD).

What do computational predictors say about CDK13 p.Tyr362Cys (c.1085A>G)?

AlphaMissense predicts likely benign (score 0.3052) — an in-silico prediction, not a clinical call.

CDK13 p.Tyr362Cys

Q: What condition is associated with CDK13 p.Tyr362Cys (c.1085A>G)?

CDK13 p.Tyr362Cys (c.1085A>G) 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.1085A>G · rs748758733 · VCV2181939

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.3052	likely benign
REVEL	0.332	indeterminate
SaProt	LLR -10.61	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	24.1	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 0.00592% African / African-American · 4/67,584 alleles

Filtering AF 0.00198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00113%

Overall 0.000743% 11/1,479,588 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00592%	16,896
Admixed American	0.0049%	20,398
Ashkenazi Jewishnot grpmax-eligible	0.00438%	22,856
European (non-Finnish)	0.000355%	281,563

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.Tyr362Cys
Coding: c.1085A>G
MANE Select: NM_003718
dbSNP: rs748758733
Type: single nucleotide variant
Location: chr7:39951726 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 362: 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-tyr362cys (accessed [today's date]).

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