RTN2 p.Glu50del
c.142GAG[2] · rs767238040 · VCV967433
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0583%, amr)
Conditions
1
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 18.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0583%
Admixed American · 35/59,988 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.00347%
56/1,613,688 alleles · ultra-rare
exomes 43/1,461,538 · genomes 13/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0583% | 1,714 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,942 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,800 |
| African / African-American | 0.00267% | 37,458 |
| European (non-Finnish) | 0.000593% | 168,574 |
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.Glu50del
- Coding
- c.142GAG[2]
- MANE Select
- NM_005619
- dbSNP
- rs767238040
- Type
- Microsatellite
- Location
- chr19:45494935 (GRCh38)
- Gene constraint
- LOEUF 0.748 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.99
- Residue 50
- 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.Glu50Ter Pathogenic/Likely pathogenic ★★ same residue
- RTN2 p.541KA[1] Uncertain significance ★ same condition
- RTN2 p.Gly57fs Pathogenic/Likely pathogenic ★★ same condition
- RTN2 c.1497+3G>A Uncertain significance ★★ same condition
- RTN2 p.Ala529Thr Uncertain significance ★★ ⚠ same condition
- RTN2 p.Arg152Pro Uncertain significance ★★ ⚠ same condition
- RTN2 p.Arg252Trp Uncertain significance ★★ ⚠ same condition
- RTN2 p.Arg398Cys 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/rtn2-p-glu50del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown