PYROXD1 p.Phe185=
c.555C>T · rs146792991 · VCV729181
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.86%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.7 | GERP -3.8 |
| Overall | ||
| CADD | 13.99 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.86%
African / African-American · 1,365/73,378 alleles
Filtering AF
1.78%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.75%
Overall
0.107%
1,682/1,570,102 alleles · low-frequency
exomes 826/1,418,086 · genomes 856/152,016 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.86% | 54 |
| Middle Eastern | 0.396% | 252 |
| Admixed American | 0.15% | 667 |
| Remaining individualsnot grpmax-eligible | 0.143% | 700 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0211% | 4,733 |
| South Asian | 0.0178% | 5,632 |
| European (non-Finnish) | 0.00916% | 10,920 |
| East Asian | 0.00232% | 43,138 |
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.Phe185=
- Coding
- c.555C>T
- MANE Select
- NM_024854
- dbSNP
- rs146792991
- Type
- single nucleotide variant
- Location
- chr12:21455198 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.64 · 2 PDB
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-phe185 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown