Is CDK13 p.Gly684Val (c.2051G>T) pathogenic?

CDK13 p.Gly684Val (c.2051G>T) is classified Uncertain significance in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely pathogenic (0.7387); Very rare (popmax 0.00111%, sas); Associated with Inborn genetic diseases.

What condition is associated with CDK13 p.Gly684Val (c.2051G>T)?

CDK13 p.Gly684Val (c.2051G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK13 p.Gly684Val (c.2051G>T) in the general population?

CDK13 p.Gly684Val (c.2051G>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about CDK13 p.Gly684Val (c.2051G>T)?

AlphaMissense predicts likely pathogenic (score 0.7387) — an in-silico prediction, not a clinical call.

CDK13 p.Gly684Val

c.2051G>T · VCV3999577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7387	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 81 kb · p 2.9e-34 · regional, not allelic
Overall
CADD	29.4	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 0.00111% South Asian · 1/90,032 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000343% 5/1,456,296 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,032
European (non-Finnish)	0.00034%	294,442

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.Gly684Val
Coding: c.2051G>T
MANE Select: NM_003718
Type: single nucleotide variant
Location: chr7:39999369 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 684: 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.Gly684= Likely benign ★ same residue
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

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-gly684val (accessed [today's date]).

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