Is CDK13 p.Ser153Phe (c.458C>T) pathogenic?

CDK13 p.Ser153Phe (c.458C>T) is classified Conflicting classifications of pathogenicity in CDK13 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.8576); Ultra-rare (popmax 0.0126%, amr).

How common is CDK13 p.Ser153Phe (c.458C>T) in the general population?

CDK13 p.Ser153Phe (c.458C>T) is ultra-rare (popmax 0.0126%, amr) (gnomAD).

What do computational predictors say about CDK13 p.Ser153Phe (c.458C>T)?

AlphaMissense predicts likely pathogenic (score 0.8576) — an in-silico prediction, not a clinical call.

CDK13 p.Ser153Phe

c.458C>T · rs1279892568 · VCV1299064

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8576	likely pathogenic
REVEL	0.096	moderately benign-leaning
SaProt	LLR -9.18	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.56, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	24.3	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 0.0126% Admixed American · 3/23,748 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.000397% 5/1,259,216 alleles · ultra-rare exomes 1/1,107,132 · genomes 4/152,084 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0126%	7,916
Remaining individualsnot grpmax-eligible	0.00425%	23,549

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.Ser153Phe
Coding: c.458C>T
MANE Select: NM_003718
dbSNP: rs1279892568
Type: single nucleotide variant
Location: chr7:39951099 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 153: the 'disordered' region

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

Similar variants

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
CDK13 p.Asn842Ser 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-ser153phe (accessed [today's date]).

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