RTN2 p.Leu386=
c.1156T>C · rs1599908114 · VCV737157
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, 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 -0.27 | GERP -3.6 |
| Overall | ||
| CADD | 5.078 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,178,614 alleles
Overall
6.21e-05%
1/1,610,704 alleles · very rare
exomes 1/1,458,532 · genomes 0/152,172 · joint denominator
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.Leu386=
- Coding
- c.1156T>C
- MANE Select
- NM_005619
- dbSNP
- rs1599908114
- Type
- single nucleotide variant
- Location
- chr19:45489431 (GRCh38)
- Gene constraint
- LOEUF 0.748 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.99
- Residue 386
- 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.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
- RTN2 p.Arg406Trp Uncertain significance ★★ ⚠ same type
- RTN2 p.Arg447Gln 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-leu386 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown