MAGEL2 p.Pro91=
c.273G>A · rs374554976 · VCV1228776
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.455%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.2 | GERP 0.12, phastCons 1 |
| Overall | ||
| CADD | 14.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.455%
South Asian · 381/83,746 alleles
Filtering AF
0.417%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.402%
Overall
0.0279%
428/1,533,596 alleles · rare
exomes 405/1,381,362 · genomes 23/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.455% | 220 |
| Middle Eastern | 0.118% | 849 |
| Remaining individualsnot grpmax-eligible | 0.0234% | 4,277 |
| Admixed American | 0.0079% | 12,666 |
| European (non-Finnish) | 0.00192% | 52,080 |
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
- MAGEL2
- Protein
- p.Pro91=
- Coding
- c.273G>A
- MANE Select
- NM_019066
- dbSNP
- rs374554976
- Type
- single nucleotide variant
- Location
- chr15:23647470 (GRCh38)
- Structure
- AlphaFold pLDDT 44.28 · 1 PDB
Similar variants
- MAGEL2 p.Pro91Leu Uncertain significance ★ ⚠ same residue
- MAGEL2 p.Pro91Ser Uncertain significance ★ ⚠ same residue
- MAGEL2 p.Arg1187Ter Likely pathogenic ★★ same type
- MAGEL2 p.Gln1042Ter Pathogenic ★★ same type
- MAGEL2 p.Gln636Ter Pathogenic ★★ same type
- MAGEL2 p.Gln638Ter Pathogenic/Likely pathogenic ★★ same type
- MAGEL2 p.Gln644Ter Pathogenic/Likely pathogenic ★★ same type
- MAGEL2 p.Gln666Ter 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/magel2-p-pro91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown