RUSC2 p.Pro750=
c.2250G>A · rs373218246 · VCV1528575
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, nfe)
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 -4.5 | GERP -3.3 |
| Overall | ||
| CADD | 0.236 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
European (non-Finnish) · 182/1,180,008 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.0123%
198/1,613,614 alleles · ultra-rare
exomes 184/1,461,408 · genomes 14/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0154% | 6,484 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,413 |
| East Asian | 0.00891% | 11,225 |
| African / African-American | 0.00801% | 12,489 |
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.Pro750=
- Coding
- c.2250G>A
- MANE Select
- NM_014806
- dbSNP
- rs373218246
- Type
- single nucleotide variant
- Location
- chr9:35555295 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 45.82 · 1 PDB
- Residue 750
- the 'disordered' region
Similar variants
- RUSC2 p.Pro750Leu 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
- RUSC2 p.Ala745Thr 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-pro750 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown