DUOX2 p.Arg512=
c.1536G>A · rs752704146 · VCV1991946
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0944%, sas)
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 -0.83 | GERP 0.68, phastCons 0.003 |
| Overall | ||
| CADD | 7.803 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0944%
South Asian · 86/91,084 alleles
Filtering AF
0.0782%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0723%
Overall
0.00539%
87/1,613,946 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0944% | 1,059 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
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
- DUOX2
- Protein
- p.Arg512=
- Coding
- c.1536G>A
- MANE Select
- NM_001363711
- dbSNP
- rs752704146
- Type
- single nucleotide variant
- Location
- chr15:45108085 (GRCh38)
- Gene constraint
- LOEUF 1.165 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37
- Residue 512
- the 'peroxidase-like; mediates peroxidase activity' region; a disulfide bond
Similar variants
- DUOX2 p.Arg512Trp Uncertain significance ★★ ⚠ same residue
- DUOX2 p.Arg512Gln Uncertain significance ★ ⚠ same residue
- DUOX2 c.1040+1G>T Likely pathogenic ★★ same type
- DUOX2 c.1831+2T>G Likely pathogenic ★★ same type
- DUOX2 c.2335-1G>C Pathogenic/Likely pathogenic ★★ same type
- DUOX2 c.2560+2T>C Likely pathogenic ★★ same type
- DUOX2 c.3006-2A>G Likely pathogenic ★★ same type
- DUOX2 c.3415+1G>C 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/duox2-p-arg512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown