PYROXD1 p.Thr281=
c.843T>C · rs143417761 · VCV1563775
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.492%, eas)
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 0.92 | GERP 0.45, phastCons 0.72 |
| Overall | ||
| CADD | 3.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.492%
East Asian · 216/43,892 alleles
Filtering AF
0.438%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.418%
Overall
0.0227%
360/1,588,034 alleles · rare
exomes 288/1,435,794 · genomes 72/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.492% | 203 |
| Remaining individualsnot grpmax-eligible | 0.0587% | 1,703 |
| South Asian | 0.0577% | 1,732 |
| African / African-American | 0.0459% | 2,181 |
| Middle Eastern | 0.0176% | 5,676 |
| European (non-Finnish) | 0.00197% | 50,781 |
| Admixed American | 0.00176% | 56,702 |
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.Thr281=
- Coding
- c.843T>C
- MANE Select
- NM_024854
- dbSNP
- rs143417761
- Type
- single nucleotide variant
- Location
- chr12:21461117 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.64 · 2 PDB
- Residue 281
- an α-helix
Similar variants
- 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.Ala393Val Uncertain significance ★★ ⚠ 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-thr281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown