RTN4IP1 p.Pro149=
c.447T>C · rs376863354 · VCV2779163
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00483%, 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 -0.3 | GERP -4.8, phastCons 0.007 |
| Overall | ||
| CADD | 6.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00483%
European (non-Finnish) · 57/1,179,948 alleles
Filtering AF
0.00378%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00345%
Overall
0.00353%
57/1,613,860 alleles · very rare
exomes 56/1,461,718 · genomes 1/152,142 · 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
- RTN4IP1
- Protein
- p.Pro149=
- Coding
- c.447T>C
- MANE Select
- NM_032730
- dbSNP
- rs376863354
- Type
- single nucleotide variant
- Location
- chr6:106621473 (GRCh38)
- Gene constraint
- LOEUF 0.952 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 1 PDB
- Residue 149
- the enoyl reductase (er) domain; a UniProt-annotated variant site (in opa10)
Similar variants
- RTN4IP1 p.Pro149Ala Uncertain significance ★ ⚠ same residue
- RTN4IP1 p.Pro149Leu Uncertain significance ★ same residue
- 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
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-pro149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown