RTN2 p.Cys389Ter
c.1167C>A · rs758370815 · VCV1073870
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 11 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.6 |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- RTN2
- Protein
- p.Cys389Ter
- Coding
- c.1167C>A
- MANE Select
- NM_005619
- dbSNP
- rs758370815
- Type
- single nucleotide variant
- Location
- chr19:45489420 (GRCh38)
- Gene constraint
- LOEUF 0.748 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.99
- Residue 389
- a UniProt-annotated variant site (in hmnr11; likely pathogenic); a UniProt-annotated variant site (in spg12; likely pathogenic); the reticulon domain
Similar variants
- RTN2 p.Cys389= Likely benign ★★ same residue
- RTN2 p.Glu50Ter 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
- RTN2 p.Arg447Gln 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-cys389ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown