Is CDK13 p.Ser231Ala (c.691T>G) pathogenic?

CDK13 p.Ser231Ala (c.691T>G) is classified Benign in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0993); Very rare (popmax 0.00279%, amr).

How common is CDK13 p.Ser231Ala (c.691T>G) in the general population?

CDK13 p.Ser231Ala (c.691T>G) is very rare (popmax 0.00279%, amr) (gnomAD).

What do computational predictors say about CDK13 p.Ser231Ala (c.691T>G)?

AlphaMissense predicts likely benign (score 0.0993) — an in-silico prediction, not a clinical call.

CDK13 p.Ser231Ala

c.691T>G · VCV4748256

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00279%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0993	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -8.10	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 1.9	GERP 0.57, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	15.93	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 0.00279% Admixed American · 1/35,858 alleles

Overall 7.75e-05% 1/1,289,610 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.Ser231Ala
Coding: c.691T>G
MANE Select: NM_003718
Type: single nucleotide variant
Location: chr7:39951332 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 231: the 'disordered' region

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

Similar variants

CDK13 p.Ser231= 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
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-ser231ala (accessed [today's date]).

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