NOX4 p.Pro224=
c.672C>T · rs140381222 · VCV722792
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.147%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.44 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 6.705 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.147%
European (non-Finnish) · 1,732/1,179,054 alleles
Filtering AF
0.141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.139%
Overall
0.118%
1,898/1,611,256 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.147% | 681 |
| Remaining individualsnot grpmax-eligible | 0.106% | 945 |
| Admixed American | 0.0925% | 1,081 |
| Middle Eastern | 0.083% | 1,205 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0272% | 3,673 |
| African / African-American | 0.0187% | 5,344 |
| South Asian | 0.0155% | 6,465 |
| East Asian | 0.00446% | 22,410 |
| Finnishnot grpmax-eligible | 0.00313% | 31,975 |
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
- NOX4
- Protein
- p.Pro224=
- Coding
- c.672C>T
- MANE Select
- NM_016931
- dbSNP
- rs140381222
- Type
- single nucleotide variant
- Location
- chr11:89402500 (GRCh38)
- Gene constraint
- LOEUF 1.018 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.98
- Residue 224
- the ferric oxidoreductase domain; the 'e-loop; essential for h2o2 generating catalytic activity' region
Similar variants
- NOX4 c.1218-6C>T Benign ★★ same type
- NOX4 p.Arg470Cys Benign ★★ same type
- NOX4 p.Arg95= Likely benign ★★ same type
- NOX4 p.Leu97Phe Likely benign ★★ same type
- NOX4 p.Ala10Thr Uncertain significance ★ ⚠ same type
- NOX4 p.Ala333Thr Uncertain significance ★ ⚠ same type
- NOX4 p.Arg231Gln Uncertain significance ★ ⚠ same type
- NOX4 p.Arg304Trp 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/nox4-p-pro224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown