Is CDK5RAP2 p.Arg384His (c.1151G>A) pathogenic?

CDK5RAP2 p.Arg384His (c.1151G>A) is classified Uncertain significance in CDK5RAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.0659); Very rare (popmax 0.00669%, eas).

How common is CDK5RAP2 p.Arg384His (c.1151G>A) in the general population?

CDK5RAP2 p.Arg384His (c.1151G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Arg384His (c.1151G>A)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Arg384His

c.1151G>A · rs764922734 · VCV2054585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.02	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 -2	GERP -5.2
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	0.699	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 0.00669% East Asian · 3/44,852 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00161% 26/1,613,524 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,951
South Asian	0.00659%	15,167
Remaining individualsnot grpmax-eligible	0.0048%	20,822
Admixed American	0.00334%	29,956
European (non-Finnish)	0.00102%	98,331

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: CDK5RAP2
Protein: p.Arg384His
Coding: c.1151G>A
MANE Select: NM_018249
dbSNP: rs764922734
Type: single nucleotide variant
Location: chr9:120518587 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 5 PDB

Full CDK5RAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK5RAP2 p.Arg384Cys Uncertain significance ★ ⚠ same residue
CDK5RAP2 c.4005-1G>A Pathogenic ★★ same type
CDK5RAP2 c.4963+1G>A Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1403Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same type
CDK5RAP2 p.Arg1558Ter Pathogenic ★★ same type
CDK5RAP2 p.Arg427Ter Pathogenic ★★ same type
CDK5RAP2 p.Gln1301Ter 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/cdk5rap2-p-arg384his (accessed [today's date]).

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