PPOX p.Gln421=
c.1263G>A · rs370738994 · VCV1621521
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00737%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.231 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 0.48, phastCons 1 |
| Overall | ||
| CADD | 4.845 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00737%
European (non-Finnish) · 87/1,180,048 alleles
Filtering AF
0.00605%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00565%
Overall
0.00564%
91/1,613,910 alleles · very rare
exomes 82/1,461,772 · genomes 9/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00737% | 13,564 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
| African / African-American | 0.00134% | 74,900 |
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.Gln421=
- Coding
- c.1263G>A
- MANE Select
- NM_001122764
- dbSNP
- rs370738994
- Type
- single nucleotide variant
- Location
- chr1:161170921 (GRCh38)
- Gene constraint
- LOEUF 0.581 · pLI 0.24 (gnomAD)
- Structure
- AlphaFold pLDDT 95.39 · 3 PDB
Similar variants
- PPOX p.Gln421His Uncertain significance ★★ ⚠ same residue
- 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
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-gln421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown