CDK5RAP2 p.Arg591Gln
c.1772G>A · rs749612238 · VCV374241
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1042 | likely benign |
|---|---|---|
| REVEL | 0.099 | moderately benign-leaning |
| SaProt | LLR -4.74 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | Δ0.99 | acceptor gain · deltas |
| Pangolin | Δ0.86 | gain · loss 0.61 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1.2, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 191 kb · p 0.44 · regional, not allelic |
| Overall | ||
| CADD | 35.0 | 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
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| East Asiangrpmax | 0.00223% | 44,878 |
| South Asian | 0.0022% | 45,534 |
| European (non-Finnish) | 0.00178% | 56,179 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
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.Arg591Gln
- Coding
- c.1772G>A
- MANE Select
- NM_018249
- dbSNP
- rs749612238
- Type
- single nucleotide variant
- Location
- chr9:120471834 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 60.11 · 5 PDB
Similar variants
- CDK5RAP2 p.Arg591Trp 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-arg591gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown