Is CDK13 p.Ala309Val (c.926C>T) pathogenic?

CDK13 p.Ala309Val (c.926C>T) is classified Uncertain significance in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). AlphaMissense: likely benign (0.2944); Very rare (popmax 0.00282%, afr).

How common is CDK13 p.Ala309Val (c.926C>T) in the general population?

CDK13 p.Ala309Val (c.926C>T) is very rare (popmax 0.00282%, afr) (gnomAD).

What do computational predictors say about CDK13 p.Ala309Val (c.926C>T)?

AlphaMissense predicts likely benign (score 0.2944) — an in-silico prediction, not a clinical call.

CDK13 p.Ala309Val

c.926C>T · rs746519649 · VCV2797826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00282%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2944	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -7.50	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 7.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.00282% African / African-American · 2/70,898 alleles

Filtering AF 0.000468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000175%

Overall 0.000437% 6/1,371,592 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00282%	35,449
South Asian	0.00123%	81,244
European (non-Finnish)	0.000264%	379,272

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.Ala309Val
Coding: c.926C>T
MANE Select: NM_003718
dbSNP: rs746519649
Type: single nucleotide variant
Location: chr7:39951567 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 309: the 'disordered' region

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

Similar variants

CDK13 p.Ala309Thr Uncertain significance ★ ⚠ same residue
CDK13 p.Ala309= Likely benign ★ 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

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-ala309val (accessed [today's date]).

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