Is CDK5 p.Arg120His (c.359G>A) pathogenic?

CDK5 p.Arg120His (c.359G>A) is classified Uncertain significance in CDK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.1743); Very rare (popmax 0.00133%, afr).

How common is CDK5 p.Arg120His (c.359G>A) in the general population?

CDK5 p.Arg120His (c.359G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CDK5 p.Arg120His (c.359G>A)?

AlphaMissense predicts likely benign (score 0.1743) — an in-silico prediction, not a clinical call.

CDK5 p.Arg120His

c.359G>A · rs770858106 · VCV2602938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1743	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.25	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 803 bp · p 0.67 · regional, not allelic
Overall
CADD	22.5	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 0.00133% African / African-American · 1/74,990 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,459,710 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,990
European (non-Finnish)	0.000424%	235,779

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.Arg120His
Coding: c.359G>A
MANE Select: NM_004935
dbSNP: rs770858106
Type: single nucleotide variant
Location: chr7:151055802 (GRCh38)
Gene constraint: LOEUF 0.584 · pLI 0.56 (gnomAD)
Structure: AlphaFold pLDDT 91.83 · 12 PDB
Residue 120: the protein kinase domain

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

Similar variants

CDK5 p.Arg120Cys 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.Pro240= Likely benign ★★ same type
CDK5 p.Ser72= Benign/Likely 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-arg120his (accessed [today's date]).

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