Is CDK13 p.Pro126Leu (c.377C>T) pathogenic?

CDK13 p.Pro126Leu (c.377C>T) is classified Benign in CDK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: likely benign (0.1176); Very rare (popmax 0.0024%, sas).

How common is CDK13 p.Pro126Leu (c.377C>T) in the general population?

CDK13 p.Pro126Leu (c.377C>T) is very rare (popmax 0.0024%, sas) (gnomAD).

What do computational predictors say about CDK13 p.Pro126Leu (c.377C>T)?

AlphaMissense predicts likely benign (score 0.1176) — an in-silico prediction, not a clinical call.

CDK13 p.Pro126Leu

c.377C>T · rs1477767717 · VCV1978649

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1176 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0024%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1176	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.26	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 0.56, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0024% South Asian · 1/41,678 alleles

Filtering AF 0.000335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000242%

Overall 0.000785% 9/1,147,084 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0024%	41,678
European (non-Finnish)	0.000779%	128,319

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.Pro126Leu
Coding: c.377C>T
MANE Select: NM_003718
dbSNP: rs1477767717
Type: single nucleotide variant
Location: chr7:39951018 (GRCh38)
Gene constraint: LOEUF 0.434 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 50.59 · 2 PDB
Residue 126: the 'disordered' region

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

Similar variants

CDK13 p.Pro126Gln Uncertain significance ★ ⚠ same residue
CDK13 p.Pro126Ser Uncertain significance ★ ⚠ 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-pro126leu (accessed [today's date]).

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