PYROXD1 p.Ala393=
c.1179G>A · rs146542607 · VCV1571225
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0694%, afr)
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 -1.7 | GERP -3.8 |
| Overall | ||
| CADD | 1.987 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0694%
African / African-American · 52/74,874 alleles
Filtering AF
0.0544%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.049%
Overall
0.0041%
66/1,611,602 alleles · ultra-rare
exomes 32/1,459,564 · genomes 34/152,038 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0694% | 1,440 |
| Admixed American | 0.01% | 9,980 |
| East Asian | 0.00223% | 44,810 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,398 |
| South Asian | 0.0011% | 90,918 |
| European (non-Finnish) | 0.000424% | 235,673 |
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
- PYROXD1
- Protein
- p.Ala393=
- Coding
- c.1179G>A
- MANE Select
- NM_024854
- dbSNP
- rs146542607
- Type
- single nucleotide variant
- Location
- chr12:21467543 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.64 · 2 PDB
- Residue 393
- an α-helix
Similar variants
- PYROXD1 p.Ala393Val Uncertain significance ★★ ⚠ same residue
- PYROXD1 c.285+1G>A Pathogenic/Likely pathogenic ★★ same type
- PYROXD1 c.881-2A>T Likely pathogenic ★★ same type
- PYROXD1 p.Asn155Ser Pathogenic ★★ same type
- PYROXD1 p.Arg132Cys Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Arg455Gln Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Arg76Cys Uncertain significance ★★ ⚠ same type
- PYROXD1 p.Asn52Asp 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/pyroxd1-p-ala393 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown