DNASE1 p.Pro249=
c.747C>T · rs201975812 · VCV712625
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.398%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.35 | acceptor loss, 42 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.48 | gain · loss 0.43 · SpliceAI calls loss · independent |
| Constraint at this position | ||
| Conservation | phyloP -9.5 | GERP -3.2 |
| Overall | ||
| CADD | 1.753 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.398%
Admixed American · 239/60,010 alleles
Filtering AF
0.357%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.341%
Overall
0.0196%
316/1,613,906 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.398% | 251 |
| South Asian | 0.0351% | 2,846 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,417 |
| African / African-American | 0.004% | 25,010 |
| European (non-Finnish) | 0.00297% | 33,712 |
| East Asian | 0.00223% | 44,884 |
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
- DNASE1
- Protein
- p.Pro249=
- Coding
- c.747C>T
- MANE Select
- NM_005223
- dbSNP
- rs201975812
- Type
- single nucleotide variant
- Location
- chr16:3657762 (GRCh38)
- Gene constraint
- LOEUF 1.46 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 94.68 · 1 PDB
Similar variants
- DNASE1 p.Asn40Ser Uncertain significance ★★ ⚠ same type
- DNASE1 p.Val21Met Uncertain significance ★★ ⚠ same type
- TRAP1 p.Ala465Gly Uncertain significance ★★ ⚠ same type
- TRAP1 p.Ala474Val Uncertain significance ★★ ⚠ same type
- TRAP1 p.Ala608Ser Uncertain significance ★★ ⚠ same type
- TRAP1 p.Ala628Val Uncertain significance ★★ ⚠ same type
- TRAP1 p.Ala659Val Uncertain significance ★★ ⚠ same type
- TRAP1 p.Ala676Val 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/dnase1-p-pro249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown