MAGEL2 p.Ala554=
c.1662G>A · rs910557950 · VCV1905790
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00248%, amr)
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 -4.4 | GERP -2.5 |
| Overall | ||
| CADD | 5.699 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00248%
Admixed American · 1/40,376 alleles
Overall
0.000204%
3/1,468,232 alleles · very rare
exomes 1/1,317,312 · genomes 2/150,920 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00248% | 40,376 |
| African / African-American | 0.00144% | 69,426 |
| South Asian | 0.00137% | 73,108 |
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.Ala554=
- Coding
- c.1662G>A
- MANE Select
- NM_019066
- dbSNP
- rs910557950
- Type
- single nucleotide variant
- Location
- chr15:23646081 (GRCh38)
- Structure
- AlphaFold pLDDT 44.28 · 1 PDB
- Residue 554
- the 'disordered' region
Similar variants
- MAGEL2 p.Ala554Gly 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
- MAGEL2 p.Trp686Ter 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-ala554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown