DUOX2 p.Pro1253=
c.3759G>A · rs140663764 · VCV316145
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.72 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.4 |
| Overall | ||
| CADD | 14.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 3.53% | 28 |
| Middle Easterngrpmax | 2.79% | 36 |
| South Asian | 1.59% | 63 |
| Remaining individualsnot grpmax-eligible | 0.726% | 138 |
| Admixed American | 0.323% | 309 |
| European (non-Finnish) | 0.265% | 377 |
| African / African-American | 0.0493% | 2,029 |
| Finnishnot grpmax-eligible | 0.0203% | 4,926 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Pro1253=
- Coding
- c.3759G>A
- MANE Select
- NM_001363711
- dbSNP
- rs140663764
- Type
- single nucleotide variant
- Location
- chr15:45097326 (GRCh38)
- Gene constraint
- LOEUF 1.165 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37
- Residue 1253
- the ferric oxidoreductase domain
Disease context
thyroid dyshormonogenesis 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Genetic transient congenital hypothyroidism (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- DUOX2 p.Pro1253Leu Uncertain significance ★★ ⚠ same residue
- DUOX2 c.1831+2T>G Likely pathogenic ★★ same condition
- DUOX2 c.2335-1G>C Pathogenic/Likely pathogenic ★★ same condition
- DUOX2 c.2560+2T>C Likely pathogenic ★★ same condition
- DUOX2 c.3006-2A>G Likely pathogenic ★★ same condition
- DUOX2 c.3693+1G>T Pathogenic/Likely pathogenic ★★ same condition
- DUOX2 c.4081-1G>A Likely pathogenic ★★ same condition
- DUOX2 c.4239+1G>A Likely pathogenic ★★ same condition
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-pro1253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown