DUOX2 p.Ala554=
c.1662C>T · rs1163316724 · VCV1628197
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 1.6 | GERP -2.3, phastCons 1 |
| Overall | ||
| CADD | 7.143 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,004 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000558%
9/1,614,116 alleles · very rare
exomes 7/1,461,890 · genomes 2/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,002 |
| East Asian | 0.00223% | 44,898 |
| South Asian | 0.0011% | 91,094 |
| European (non-Finnish) | 0.000424% | 236,012 |
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.Ala554=
- Coding
- c.1662C>T
- MANE Select
- NM_001363711
- dbSNP
- rs1163316724
- Type
- single nucleotide variant
- Location
- chr15:45107376 (GRCh38)
- Gene constraint
- LOEUF 1.165 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37
- Residue 554
- the 'peroxidase-like; mediates peroxidase activity' region
Similar variants
- DUOX2 p.Ala554Val 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
- DUOX2 c.3516-1G>C 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/duox2-p-ala554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown