RTN4 p.Pro992=
c.2976A>G · rs111958278 · VCV791854
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.774%, afr)
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 0.47 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 7.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.774%
African / African-American · 580/74,922 alleles
Filtering AF
0.722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.701%
Overall
0.049%
791/1,612,684 alleles · rare
exomes 450/1,460,368 · genomes 341/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.774% | 129 |
| Remaining individualsnot grpmax-eligible | 0.146% | 686 |
| Admixed American | 0.1% | 996 |
| Middle Eastern | 0.0498% | 2,008 |
| European (non-Finnish) | 0.00466% | 21,443 |
| South Asian | 0.0022% | 45,428 |
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
- RTN4
- Protein
- p.Pro992=
- Coding
- c.2976A>G
- MANE Select
- NM_020532
- dbSNP
- rs111958278
- Type
- single nucleotide variant
- Location
- chr2:55025123 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.38 (gnomAD)
- Structure
- AlphaFold pLDDT 40.92 · 2 PDB
Similar variants
- RTN4 p.Glu899Gln Benign ★★ same type
- RTN4 p.Gly1070Ala Likely benign ★★ same type
- RTN4 p.Leu620= Benign ★★ same type
- RTN4 p.Leu814Met Likely benign ★★ same type
- RTN4 p.Ser440Asn Benign ★★ same type
- RTN4 p.Ser920Cys Benign ★★ same type
- RTN4 p.Thr450Met Benign ★★ same type
- RTN4 p.Ala1046Ser 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/rtn4-p-pro992 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown