Is CDK5 p.Pro240= (c.720G>T) pathogenic?

CDK5 p.Pro240= (c.720G>T) is classified Likely benign in CDK5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-14). Ultra-rare (popmax 0.0822%, mid).

How common is CDK5 p.Pro240= (c.720G>T) in the general population?

CDK5 p.Pro240= (c.720G>T) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

CDK5 p.Pro240=

c.720G>T · rs62490285 · VCV434642

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.8	GERP -3.2
Overall
CADD	4.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,082 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00607% 98/1,613,518 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,216
South Asian	0.0439%	2,276
Remaining individualsnot grpmax-eligible	0.0064%	15,614
European (non-Finnish)	0.00407%	24,578
African / African-American	0.00134%	74,846

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: CDK5
Protein: p.Pro240=
Coding: c.720G>T
MANE Select: NM_004935
dbSNP: rs62490285
Type: single nucleotide variant
Location: chr7:151054284 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 91.83 · 12 PDB
Residue 240: the protein kinase domain; an α-helix

Full CDK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK5 p.Pro240Leu Uncertain significance ★ ⚠ same residue
CDK5 p.Met230Val Uncertain significance ★★ ⚠ same type
CDK5 c.194+12G>A Benign/Likely benign ★★ same type
CDK5 c.312+3G>A Benign ★★ same type
CDK5 c.408+9T>C Likely benign ★★ same type
CDK5 c.483+11A>C Benign ★★ same type
CDK5 p.Ser72= Benign/Likely benign ★★ same type
CDK5 p.Arg50Gln 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/cdk5-p-pro240 (accessed [today's date]).

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