Is CDK13 p.Gly161Ala (c.482G>C) pathogenic?

CDK13 p.Gly161Ala (c.482G>C) is classified Conflicting classifications of pathogenicity in CDK13 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0655); Very rare (popmax 0.00201%, nfe); Associated with CDK13-related disorder.

What condition is associated with CDK13 p.Gly161Ala (c.482G>C)?

CDK13 p.Gly161Ala (c.482G>C) is associated with CDK13-related disorder (ClinVar).

How common is CDK13 p.Gly161Ala (c.482G>C) in the general population?

CDK13 p.Gly161Ala (c.482G>C) is very rare (popmax 0.00201%, nfe) (gnomAD).

What do computational predictors say about CDK13 p.Gly161Ala (c.482G>C)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

CDK13 p.Gly161Ala

c.482G>C · rs902803165 · VCV2628627

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00201%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDK13-related disorder

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.70	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 6.5	GERP -0.53, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	19.27	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 0.00201% European (non-Finnish) · 20/995,164 alleles

Filtering AF 0.00131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00107%

Overall 0.00161% 20/1,243,872 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.Gly161Ala
Coding: c.482G>C
MANE Select: NM_003718
dbSNP: rs902803165
Type: single nucleotide variant
Location: chr7:39951123 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 161: the 'disordered' region

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

Disease context

CDK13-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK13 p.Gly161Val Uncertain significance ★★ ⚠ same residue
CDK13 p.Gly161Glu Uncertain significance ★ ⚠ same residue
CDK13 p.Gly161= Likely benign ★ same residue
CDK13 p.Gly161Trp Benign ★ ⚠ same residue
CDK13 p.Lys734Arg Pathogenic/Likely pathogenic ★★ same condition
CDK13 p.Thr876Ile Likely pathogenic ★★ same condition
CDK13 p.Tyr870Cys Likely pathogenic ★★ same condition
CDK13 p.Asp797His 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-gly161ala (accessed [today's date]).

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