Is CDK13 p.Ala622Val (c.1865C>T) pathogenic?

CDK13 p.Ala622Val (c.1865C>T) is classified Uncertain significance in CDK13 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0866); Very rare (popmax 0.00116%, sas); Associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder.

How common is CDK13 p.Ala622Val (c.1865C>T) in the general population?

CDK13 p.Ala622Val (c.1865C>T) is very rare (popmax 0.00116%, sas) (gnomAD).

What do computational predictors say about CDK13 p.Ala622Val (c.1865C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

CDK13 p.Ala622Val

Q: What condition is associated with CDK13 p.Ala622Val (c.1865C>T)?

CDK13 p.Ala622Val (c.1865C>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.1865C>T · VCV3377597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00116%, 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	0.0866	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -6.38	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 4.8	GERP 1.8, phastCons 0.53
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00116% South Asian · 1/86,512 alleles

Overall 0.000139% 2/1,438,784 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00116%	86,512
European (non-Finnish)	8.52e-05%	1,173,354

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.Ala622Val
Coding: c.1865C>T
MANE Select: NM_003718
Type: single nucleotide variant
Location: chr7:39988252 (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.Ala622Asp 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-ala622val (accessed [today's date]).

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