Is CDK13 p.Ser177fs (c.527dup) pathogenic?

CDK13 p.Ser177fs (c.527dup) is classified Pathogenic/Likely pathogenic in CDK13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-27). Very rare (popmax 0.000101%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDK13 p.Ser177fs (c.527dup)?

CDK13 p.Ser177fs (c.527dup) is associated with Inborn genetic diseases (ClinVar).

How common is CDK13 p.Ser177fs (c.527dup) in the general population?

CDK13 p.Ser177fs (c.527dup) is very rare (popmax 0.000101%, nfe) (gnomAD).

CDK13 p.Ser177fs

c.527dup · VCV3342092

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000101%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 0.56, phastCons 1
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GGC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000101% European (non-Finnish) · 1/994,760 alleles

Overall 0.000658% 1/151,928 alleles · very rare

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.Ser177fs
Coding: c.527dup
MANE Select: NM_003718
Type: Duplication
Location: chr7:39951162 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 177: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK13 p.Ser385fs Pathogenic ★ same condition
CDK13 p.Val564Ter Pathogenic ★ same condition
CDK13 p.Ser177Gly Uncertain significance ★ ⚠ same residue
CDK13 p.Ser250_Ser251insGlySer Conflicting classifications of pathogenicity ★ same condition
CDK13 p.Leu61fs Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Ala1301Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala134Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala182Val Uncertain significance ★★ ⚠ 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-ser177fs (accessed [today's date]).

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