GSDMD p.Pro414=
c.1242G>A · rs146780569 · VCV736776
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.146%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.022 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -3.1 |
| Overall | ||
| CADD | 0.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.146%
African / African-American · 109/74,834 alleles
Filtering AF
0.123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.115%
Overall
0.00904%
145/1,604,252 alleles · rare
exomes 69/1,451,942 · genomes 76/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.146% | 687 |
| Admixed American | 0.0204% | 4,909 |
| Middle Eastern | 0.0166% | 6,038 |
| Remaining individualsnot grpmax-eligible | 0.00645% | 15,515 |
| East Asian | 0.00225% | 44,512 |
| Finnishnot grpmax-eligible | 0.00161% | 61,926 |
| European (non-Finnish) | 0.00145% | 69,173 |
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
- GSDMD
- Protein
- p.Pro414=
- Coding
- c.1242G>A
- MANE Select
- NM_024736
- dbSNP
- rs146780569
- Type
- single nucleotide variant
- Location
- chr8:143562691 (GRCh38)
- Gene constraint
- LOEUF 1.493 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.45 · 11 PDB
- Residue 414
- a β-strand
Similar variants
- GSDMD p.Arg249His Benign ★★ same type
- GSDMD p.Arg7= Likely benign ★★ same type
- GSDMD p.Gln396Arg Benign ★★ same type
- GSDMD p.Ser3= Benign ★★ same type
- GSDMD p.Thr453Ala Benign ★★ same type
- GSDMD p.Ala215Thr Uncertain significance ★ ⚠ same type
- GSDMD p.Ala244Val Uncertain significance ★ ⚠ same type
- GSDMD p.Ala255Thr 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/gsdmd-p-pro414 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown