Is CDK5RAP2 p.Arg150Ter (c.448C>T) pathogenic?

CDK5RAP2 p.Arg150Ter (c.448C>T) is classified Pathogenic in CDK5RAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). Very rare (popmax 0.0011%, nfe); Associated with CDK5RAP2-related disorder.

What condition is associated with CDK5RAP2 p.Arg150Ter (c.448C>T)?

CDK5RAP2 p.Arg150Ter (c.448C>T) is associated with CDK5RAP2-related disorder (ClinVar).

How common is CDK5RAP2 p.Arg150Ter (c.448C>T) in the general population?

CDK5RAP2 p.Arg150Ter (c.448C>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

CDK5RAP2 p.Arg150Ter

c.448C>T · rs771565845 · VCV2628755

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

CDK5RAP2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 38
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 2.2, phastCons 0.72
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,810 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00103% 15/1,461,610 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
Finnishnot grpmax-eligible	0.00156%	64,004
European (non-Finnish)grpmax	0.0011%	90,755

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg150Ter
Coding: c.448C>T
MANE Select: NM_018249
dbSNP: rs771565845
Type: single nucleotide variant
Location: chr9:120539100 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.11 · 5 PDB
Residue 150: the 'interaction with nckap5l' region

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

Disease context

CDK5RAP2-related disorder

Similar variants

CDK5RAP2 p.Arg150Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CDK5RAP2 p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same condition
CDK5RAP2 c.5452-8C>T Conflicting classifications of pathogenicity ★ same condition
CDK5RAP2 p.Glu225Ter Likely pathogenic same condition
CDK5RAP2 p.Ser1608Asn Uncertain significance ⚠ same condition
CDK5RAP2 p.Gln593= Likely benign same condition
CDK5RAP2 p.His1182= Likely benign same condition
CDK5RAP2 p.Pro1587= Likely benign same condition

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-arg150ter (accessed [today's date]).

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