Is CDK13 p.Arg958Ter (c.2872C>T) pathogenic?

CDK13 p.Arg958Ter (c.2872C>T) is classified Pathogenic in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-23). Very rare (popmax 0.00113%, sas).

How common is CDK13 p.Arg958Ter (c.2872C>T) in the general population?

CDK13 p.Arg958Ter (c.2872C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

CDK13 p.Arg958Ter

c.2872C>T · VCV4764284

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 14
Splicing
SpliceAI	Δ0.46	donor loss · deltas
Pangolin	Δ0.47	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,228 alleles

Overall 0.000139% 2/1,439,782 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,602
South Asiangrpmax	0.00113%	88,228

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.Arg958Ter
Coding: c.2872C>T
MANE Select: NM_003718
Type: single nucleotide variant
Location: chr7:40078096 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 958: the protein kinase domain; an α-helix

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

Similar variants

CDK13 p.Arg958Gln 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-arg958ter (accessed [today's date]).

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