Is CDK13 p.Leu48Phe (c.142C>T) pathogenic?

CDK13 p.Leu48Phe (c.142C>T) is classified Uncertain significance in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.1523); Very rare (popmax 0.00876%, nfe).

How common is CDK13 p.Leu48Phe (c.142C>T) in the general population?

CDK13 p.Leu48Phe (c.142C>T) is very rare (popmax 0.00876%, nfe) (gnomAD).

What do computational predictors say about CDK13 p.Leu48Phe (c.142C>T)?

AlphaMissense predicts likely benign (score 0.1523) — an in-silico prediction, not a clinical call.

CDK13 p.Leu48Phe

c.142C>T · rs918459117 · VCV2892994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1523 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00876%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1523	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -9.62	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 5.4	GERP 0.57, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 47 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	24.9	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 0.00876% European (non-Finnish) · 98/1,118,386 alleles

Filtering AF 0.00736% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00701% 103/1,470,364 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00876%	11,412
Remaining individualsnot grpmax-eligible	0.00528%	18,938
African / African-American	0.00147%	67,980
South Asian	0.0013%	76,976

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.Leu48Phe
Coding: c.142C>T
MANE Select: NM_003718
dbSNP: rs918459117
Type: single nucleotide variant
Location: chr7:39950783 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 48: the 'disordered' region

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

Similar variants

CDK13 p.Leu48= 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-leu48phe (accessed [today's date]).

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