RTN4IP1 p.Pro348=
c.1044A>G · rs763196079 · VCV1104434
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.6 | GERP -4 |
| Overall | ||
| CADD | 0.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
East Asian · 12/44,898 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00105%
17/1,613,658 alleles · ultra-rare
exomes 16/1,461,456 · genomes 1/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0267% | 3,742 |
| South Asian | 0.0022% | 45,530 |
| European (non-Finnish) | 0.000254% | 393,261 |
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
- RTN4IP1
- Protein
- p.Pro348=
- Coding
- c.1044A>G
- MANE Select
- NM_032730
- dbSNP
- rs763196079
- Type
- single nucleotide variant
- Location
- chr6:106583367 (GRCh38)
- Gene constraint
- LOEUF 0.952 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 1 PDB
- Residue 348
- the enoyl reductase (er) domain; a UniProt-annotated variant site (in opa10); an α-helix
Similar variants
- RTN4IP1 c.1083+2T>C Pathogenic/Likely pathogenic ★★ same type
- RTN4IP1 c.620+1G>C Likely pathogenic ★★ same type
- RTN4IP1 c.806+1G>A Pathogenic ★★ same type
- RTN4IP1 p.Arg103His Pathogenic ★★ same type
- RTN4IP1 p.Arg310Ter Pathogenic ★★ same type
- RTN4IP1 p.Lys201Ter Pathogenic ★★ same type
- RTN4IP1 p.Ser293Ter Pathogenic/Likely pathogenic ★★ same type
- RTN4IP1 p.Trp20Ter Pathogenic/Likely pathogenic ★★ 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/rtn4ip1-p-pro348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown