Is CDK13 p.His1431Arg (c.4292A>G) pathogenic?

CDK13 p.His1431Arg (c.4292A>G) is classified Uncertain significance in CDK13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-30). AlphaMissense: likely benign (0.1447); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDK13 p.His1431Arg (c.4292A>G)?

CDK13 p.His1431Arg (c.4292A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CDK13 p.His1431Arg (c.4292A>G) in the general population?

CDK13 p.His1431Arg (c.4292A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK13 p.His1431Arg (c.4292A>G)?

AlphaMissense predicts likely benign (score 0.1447) — an in-silico prediction, not a clinical call.

CDK13 p.His1431Arg

c.4292A>G · rs763881275 · VCV2657405

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1447	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -5.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,791 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK13
Protein: p.His1431Arg
Coding: c.4292A>G
MANE Select: NM_003718
dbSNP: rs763881275
Type: single nucleotide variant
Location: chr7:40094733 (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

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

Similar variants

CDK13 p.Ala1301Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala134Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala182Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala331Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala504Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Ala970Val Uncertain significance ★★ ⚠ same condition
CDK13 p.Arg1366Cys Uncertain significance ★★ ⚠ same condition
CDK13 p.Arg197Ser 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-his1431arg (accessed [today's date]).

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