GSDME p.Pro142=
c.426T>C · rs375535367 · VCV2758356
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.9 | GERP -4.2 |
| Overall | ||
| CADD | 0.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,928 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00143%
23/1,612,666 alleles · ultra-rare
exomes 15/1,460,452 · genomes 8/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,325 |
| Admixed American | 0.00333% | 30,006 |
| Finnishnot grpmax-eligible | 0.00319% | 31,341 |
| European (non-Finnish) | 0.000847% | 118,001 |
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.Pro142=
- Coding
- c.426T>C
- MANE Select
- NM_001127453
- dbSNP
- rs375535367
- Type
- single nucleotide variant
- Location
- chr7:24719197 (GRCh38)
- Gene constraint
- LOEUF 1.142 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.89 · 4 PDB
- Residue 142
- a UniProt-annotated variant site (in)
Similar variants
- GSDME p.Pro142Ala Uncertain significance ★★ ⚠ same residue
- GSDME p.Pro142Thr Benign ★★ 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-pro142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown