GSDME p.Pro68=
c.204G>A · VCV4895497
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 0.72 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 6.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,074 alleles
Filtering AF
0.00231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.0026%
42/1,612,774 alleles · ultra-rare
exomes 40/1,461,048 · genomes 2/151,726 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,074 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,226 |
| European (non-Finnish) | 0.00314% | 31,881 |
| African / African-American | 0.00268% | 37,369 |
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.Pro68=
- Coding
- c.204G>A
- MANE Select
- NM_001127453
- Type
- single nucleotide variant
- Location
- chr7:24749571 (GRCh38)
- Gene constraint
- LOEUF 1.142 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.89 · 4 PDB
Similar variants
- GSDME p.Pro68Leu Conflicting classifications of pathogenicity ★ ⚠ 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
- GSDME p.Arg108Cys 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-pro68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown