PPOX p.Ser228=
c.684A>G · rs771649689 · VCV2883271
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.044%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.063 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.013 | GERP -2.1, phastCons 0.041 |
| Overall | ||
| CADD | 8.663 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.044%
African / African-American · 33/74,942 alleles
Filtering AF
0.0322%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0281%
Overall
0.00223%
36/1,614,108 alleles · ultra-rare
exomes 14/1,461,886 · genomes 22/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.044% | 2,271 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
| Admixed American | 0.00167% | 60,004 |
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
- PPOX
- Protein
- p.Ser228=
- Coding
- c.684A>G
- MANE Select
- NM_001122764
- dbSNP
- rs771649689
- Type
- single nucleotide variant
- Location
- chr1:161169060 (GRCh38)
- Gene constraint
- LOEUF 0.581 · pLI 0.24 (gnomAD)
- Structure
- AlphaFold pLDDT 95.39 · 3 PDB
- Residue 228
- a β-strand
Similar variants
- PPOX c.-9G>A Likely pathogenic ★★ same type
- PPOX p.Arg168His Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPOX p.Arg59Trp Pathogenic ★★ same type
- PPOX p.Gln189Ter Pathogenic ★★ same type
- PPOX p.Gln435Ter Pathogenic/Likely pathogenic ★★ same type
- PPOX p.Glu133Ter Pathogenic ★★ same type
- PPOX p.Glu191Ter Pathogenic/Likely pathogenic ★★ same type
- PPOX c.471+3G>A 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/ppox-p-ser228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown