RTN2 p.Arg60=
c.180G>A · VCV3355039
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00666%, afr)
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 2.7 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 13.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
African / African-American · 5/75,044 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.000434%
7/1,612,734 alleles · very rare
exomes 7/1,460,426 · genomes 0/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00666% | 15,009 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
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
- RTN2
- Protein
- p.Arg60=
- Coding
- c.180G>A
- MANE Select
- NM_005619
- Type
- single nucleotide variant
- Location
- chr19:45494905 (GRCh38)
- Gene constraint
- LOEUF 0.748 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.99
- Residue 60
- a UniProt-annotated variant site (in hmnr11; likely pathogenic); a UniProt-annotated variant site (in spg12; likely pathogenic); the 'disordered' region
Similar variants
- RTN2 p.Arg60Trp Uncertain significance ★ ⚠ same residue
- RTN2 p.Arg60fs Pathogenic same residue
- RTN2 p.Glu50Ter Pathogenic/Likely pathogenic ★★ same type
- RTN2 c.1497+3G>A Uncertain significance ★★ same type
- RTN2 p.Ala529Thr Uncertain significance ★★ ⚠ same type
- RTN2 p.Arg152Pro Uncertain significance ★★ ⚠ same type
- RTN2 p.Arg252Trp Uncertain significance ★★ ⚠ same type
- RTN2 p.Arg398Cys 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/rtn2-p-arg60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown