RUSC2 p.Pro1449=
c.4347G>A · rs370627711 · VCV1599447
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.47%, sas)
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 -6.8 | GERP -3 |
| Overall | ||
| CADD | 0.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.47%
South Asian · 428/91,074 alleles
Filtering AF
0.433%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.419%
Overall
0.0313%
505/1,613,960 alleles · rare
exomes 464/1,461,622 · genomes 41/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.47% | 213 |
| Remaining individualsnot grpmax-eligible | 0.0464% | 2,155 |
| Middle Eastern | 0.033% | 3,031 |
| Admixed American | 0.0183% | 5,456 |
| African / African-American | 0.0133% | 7,506 |
| East Asian | 0.00668% | 14,959 |
| European (non-Finnish) | 0.00186% | 53,632 |
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.Pro1449=
- Coding
- c.4347G>A
- MANE Select
- NM_014806
- dbSNP
- rs370627711
- Type
- single nucleotide variant
- Location
- chr9:35561095 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 45.82 · 1 PDB
- Residue 1449
- the 'disordered' region; the sh3 domain; a UniProt-annotated variant site (in mrt61; uncertain significance)
Similar variants
- RUSC2 p.Pro1449Leu Uncertain significance ★★ ⚠ same residue
- RUSC2 p.Pro1449Gln 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-pro1449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown