RTN2 p.Gly57=
c.171C>T · rs1057465223 · VCV389425
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.86 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 13.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,998 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.000992%
16/1,613,076 alleles · ultra-rare
exomes 6/1,460,872 · genomes 10/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,000 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,619 |
| African / African-American | 0.00133% | 74,930 |
| European (non-Finnish) | 8.47e-05% | 1,180,030 |
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.Gly57=
- Coding
- c.171C>T
- MANE Select
- NM_005619
- dbSNP
- rs1057465223
- Type
- single nucleotide variant
- Location
- chr19:45494914 (GRCh38)
- Gene constraint
- LOEUF 0.748 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.99
- Residue 57
- 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.Gly57fs Pathogenic/Likely 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
- RTN2 p.Arg406Trp 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-gly57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown