Is CDK13 p.Ile708= (c.2124C>T) pathogenic?

CDK13 p.Ile708= (c.2124C>T) is classified Benign in CDK13 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Rare (popmax 0.534%, nfe).

How common is CDK13 p.Ile708= (c.2124C>T) in the general population?

CDK13 p.Ile708= (c.2124C>T) is rare (popmax 0.534%, nfe) (gnomAD).

CDK13 p.Ile708=

c.2124C>T · rs142726395 · VCV708669

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.534%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.75	GERP -1.9, phastCons 0.008
Overall
CADD	11.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.534% European (non-Finnish) · 6,295/1,179,126 alleles

Filtering AF 0.523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.518%

Overall 0.453% 7,311/1,612,650 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.85%	35
Ashkenazi Jewishnot grpmax-eligible	0.914%	109
European (non-Finnish)grpmax	0.534%	187
Remaining individualsnot grpmax-eligible	0.455%	220
South Asian	0.195%	514
Admixed American	0.16%	624
Finnishnot grpmax-eligible	0.155%	646
African / African-American	0.0614%	1,629
East Asian	0.0357%	2,800
Middle Eastern	0.0331%	3,024

Amish 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.Ile708=
Coding: c.2124C>T
MANE Select: NM_003718
dbSNP: rs142726395
Type: single nucleotide variant
Location: chr7:39999442 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 708: the protein kinase domain; a β-strand

Full CDK13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK13 p.Ile708del Likely pathogenic ★★ same residue
CDK13 p.Ala732Thr Likely pathogenic ★★ same type
CDK13 p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Arg737Cys Pathogenic ★★ same type
CDK13 p.Arg751Gln Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Arg860Gln Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Arg880Cys Pathogenic/Likely pathogenic ★★ same type
CDK13 p.Asn842Asp Pathogenic/Likely pathogenic ★★ same type

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-ile708 (accessed [today's date]).

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