RANBP2 p.Arg454=
c.1360C>A · VCV4956327
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00373%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 10.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00373%
European (non-Finnish) · 44/1,179,844 alleles
Filtering AF
0.00283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00252%
Overall
0.00285%
46/1,611,776 alleles · very rare
exomes 38/1,459,686 · genomes 8/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00373% | 26,815 |
| Admixed American | 0.00167% | 59,982 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,288 |
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
- RANBP2
- Protein
- p.Arg454=
- Coding
- c.1360C>A
- MANE Select
- NM_006267
- Type
- single nucleotide variant
- Location
- chr2:108751350 (GRCh38)
- Gene constraint
- LOEUF 0.231 · pLI 1.00 (gnomAD)
Similar variants
- RANBP2 p.Arg454Ter Uncertain significance ★ same residue
- SOWAHC p.Lys454Thr Uncertain significance ★ ⚠ same residue
- RANBP2 p.Arg454Gln Likely benign ★ same residue
- EDAR p.Arg358Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- RANBP2 p.Thr585Met Pathogenic/Likely pathogenic ★★ ⚠ same type
- EDAR p.Leu353Phe Uncertain significance ★★ ⚠ same type
- RANBP2 c.406-2A>G Uncertain significance ★★ same type
- RANBP2 p.Ala2337Val Uncertain significance ★★ 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/ranbp2-p-arg454 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown