RTN4IP1 p.Val161=
c.483C>T · rs372723404 · VCV1117407
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0841%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor loss, 12 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.35 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 10.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0841%
African / African-American · 63/74,874 alleles
Filtering AF
0.0675%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0614%
Overall
0.00428%
69/1,613,192 alleles · ultra-rare
exomes 38/1,461,094 · genomes 31/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0841% | 1,188 |
| Admixed American | 0.005% | 19,999 |
| South Asian | 0.0022% | 45,518 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
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.Val161=
- Coding
- c.483C>T
- MANE Select
- NM_032730
- dbSNP
- rs372723404
- Type
- single nucleotide variant
- Location
- chr6:106621437 (GRCh38)
- Gene constraint
- LOEUF 0.952 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.54 · 1 PDB
- Residue 161
- the enoyl reductase (er) domain; a UniProt-annotated variant site (in opa10); a β-strand
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-val161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown