Is CDK5RAP2 p.Arg800Trp (c.2398C>T) pathogenic?

CDK5RAP2 p.Arg800Trp (c.2398C>T) is classified Uncertain significance in CDK5RAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-07). AlphaMissense: likely benign (0.1166); Ultra-rare (popmax 0.0148%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDK5RAP2 p.Arg800Trp (c.2398C>T)?

CDK5RAP2 p.Arg800Trp (c.2398C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDK5RAP2 p.Arg800Trp (c.2398C>T) in the general population?

CDK5RAP2 p.Arg800Trp (c.2398C>T) is ultra-rare (popmax 0.0148%, nfe) (gnomAD).

What do computational predictors say about CDK5RAP2 p.Arg800Trp (c.2398C>T)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

CDK5RAP2 p.Arg800Trp

c.2398C>T · rs148134702 · VCV2200617

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.043	GERP -4.9
Regional constraint	o/e 0.98	unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic
Overall
CADD	11.5	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 0.0148% European (non-Finnish) · 175/1,180,012 alleles

Filtering AF 0.013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0123%

Overall 0.0121% 196/1,614,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0148%	6,743
South Asian	0.0121%	8,281
African / African-American	0.00666%	15,005
Remaining individualsnot grpmax-eligible	0.0048%	20,837
East Asian	0.00223%	44,880
Admixed American	0.00167%	60,024

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.Arg800Trp
Coding: c.2398C>T
MANE Select: NM_018249
dbSNP: rs148134702
Type: single nucleotide variant
Location: chr9:120453851 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDK5RAP2 p.Arg800Gln Uncertain significance ★ ⚠ same residue
CDK5RAP2 c.1727+6C>G Uncertain significance ★★ same condition
CDK5RAP2 p.Ala181Ser Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala235Thr Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala326Ser Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala358Thr Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala382Val Uncertain significance ★★ ⚠ same condition
CDK5RAP2 p.Ala764Pro Uncertain significance ★★ ⚠ 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-arg800trp (accessed [today's date]).

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