GSDME p.Pro372=
c.1116G>A · VCV4747764
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.044%, afr)
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 -4.9 | GERP -3.3 |
| Overall | ||
| CADD | 0.166 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.044%
African / African-American · 33/75,068 alleles
Filtering AF
0.0321%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0281%
Overall
0.00489%
79/1,614,220 alleles · ultra-rare
exomes 54/1,461,884 · genomes 25/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.044% | 2,275 |
| South Asian | 0.0187% | 5,358 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| East Asian | 0.00223% | 44,882 |
| European (non-Finnish) | 0.00203% | 49,168 |
| Admixed American | 0.00167% | 60,036 |
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
- GSDME
- Protein
- p.Pro372=
- Coding
- c.1116G>A
- MANE Select
- NM_001127453
- Type
- single nucleotide variant
- Location
- chr7:24706251 (GRCh38)
- Gene constraint
- LOEUF 1.142 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.89 · 4 PDB
Similar variants
- GSDME p.Pro372Leu Uncertain significance ★★ ⚠ same residue
- GSDME p.Pro372fs Pathogenic same residue
- GSDME c.1183+1G>A Pathogenic/Likely pathogenic ★★ same type
- GSDME p.Ala288Glu Uncertain significance ★★ ⚠ same type
- GSDME p.Ala316Val Uncertain significance ★★ ⚠ same type
- GSDME p.Ala343Val Uncertain significance ★★ ⚠ same type
- GSDME p.Ala400Thr Uncertain significance ★★ ⚠ same type
- GSDME p.Ala422Thr 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/gsdme-p-pro372 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown