RUSC2 p.Pro833=
c.2499G>A · rs372568851 · VCV1556866
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0684%, 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 -0.76 | GERP -2.9 |
| Overall | ||
| CADD | 0.542 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0684%
Admixed American · 41/59,960 alleles
Filtering AF
0.0518%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0459%
Overall
0.00415%
67/1,613,942 alleles · ultra-rare
exomes 61/1,461,732 · genomes 6/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0684% | 1,462 |
| African / African-American | 0.00667% | 14,985 |
| South Asian | 0.00439% | 22,770 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
| European (non-Finnish) | 0.00127% | 78,668 |
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
- RUSC2
- Protein
- p.Pro833=
- Coding
- c.2499G>A
- MANE Select
- NM_014806
- dbSNP
- rs372568851
- Type
- single nucleotide variant
- Location
- chr9:35555544 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 45.82 · 1 PDB
- Residue 833
- the 'disordered' region
Similar variants
- RUSC2 p.Pro833Leu Uncertain significance ★★ ⚠ same residue
- RUSC2 p.Pro833Gln Uncertain significance ★ ⚠ same residue
- RUSC2 p.Arg1393Ter Pathogenic/Likely pathogenic ★★ same type
- RUSC2 p.Ala1054Thr Uncertain significance ★★ ⚠ same type
- RUSC2 p.Ala1268Thr Uncertain significance ★★ ⚠ same type
- RUSC2 p.Ala126Thr Uncertain significance ★★ ⚠ same type
- RUSC2 p.Ala319Thr Uncertain significance ★★ ⚠ same type
- RUSC2 p.Ala585Thr 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/rusc2-p-pro833 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown