Is CDK5 p.Arg50Gln (c.149G>A) pathogenic?

CDK5 p.Arg50Gln (c.149G>A) is classified Likely pathogenic in CDK5 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-27). AlphaMissense: likely pathogenic (0.9957); Absent from gnomAD v4.1; Associated with lissencephaly 7 with cerebellar hypoplasia.

What condition is associated with CDK5 p.Arg50Gln (c.149G>A)?

CDK5 p.Arg50Gln (c.149G>A) is associated with lissencephaly 7 with cerebellar hypoplasia (ClinVar).

How common is CDK5 p.Arg50Gln (c.149G>A) in the general population?

CDK5 p.Arg50Gln (c.149G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDK5 p.Arg50Gln (c.149G>A)?

AlphaMissense predicts likely pathogenic (score 0.9957) — an in-silico prediction, not a clinical call.

CDK5 p.Arg50Gln

c.149G>A · rs2486426172 · VCV2683824

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

lissencephaly 7 with cerebellar hypoplasia

Computational evidence

Protein change
AlphaMissense	0.9957	likely pathogenic ✓ concordant with ClinVar
REVEL	0.441	indeterminate
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP -0.55, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 1,256 bp · p 3.2e-10 · regional, not allelic
Overall
CADD	29.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDK5
Protein: p.Arg50Gln
Coding: c.149G>A
MANE Select: NM_004935
dbSNP: rs2486426172
Type: single nucleotide variant
Location: chr7:151056953 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 91.83 · 12 PDB
Residue 50: the protein kinase domain; an α-helix

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

Disease context

lissencephaly 7 with cerebellar hypoplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK5 p.Arg50= Likely benign ★ same residue
CDK5 p.Tyr179Ter Uncertain significance ★ same condition
CDK5 c.580+1G>A Pathogenic same condition
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

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-arg50gln (accessed [today's date]).

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