Is CDK13 p.Arg280Gly (c.838C>G) pathogenic?

CDK13 p.Arg280Gly (c.838C>G) is classified Uncertain significance in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-21). AlphaMissense: ambiguous (0.3666); Very rare (popmax 0.000175%, nfe).

How common is CDK13 p.Arg280Gly (c.838C>G) in the general population?

CDK13 p.Arg280Gly (c.838C>G) is very rare (popmax 0.000175%, nfe) (gnomAD).

What do computational predictors say about CDK13 p.Arg280Gly (c.838C>G)?

AlphaMissense predicts ambiguous (score 0.3666) — an in-silico prediction, not a clinical call.

CDK13 p.Arg280Gly

c.838C>G · rs1002669406 · VCV1721311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3666	ambiguous
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.28, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	23.2	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 0.000175% European (non-Finnish) · 2/1,143,046 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000144% 2/1,385,366 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.Arg280Gly
Coding: c.838C>G
MANE Select: NM_003718
dbSNP: rs1002669406
Type: single nucleotide variant
Location: chr7:39951479 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 280: the 'disordered' region

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

Similar variants

CDK13 p.Arg280Ser Uncertain significance ★ 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-arg280gly (accessed [today's date]).

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