DNASE1 p.Ala260=
c.780C>A · rs147763166 · VCV2646125
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0516%, nfe)
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 -6.9 | GERP -3 |
| Overall | ||
| CADD | 0.124 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0516%
European (non-Finnish) · 609/1,179,924 alleles
Filtering AF
0.0482%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0468%
Overall
0.0397%
640/1,613,766 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0516% | 1,937 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,675 |
| Finnishnot grpmax-eligible | 0.0125% | 7,984 |
| African / African-American | 0.00668% | 14,980 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
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.Ala260=
- Coding
- c.780C>A
- MANE Select
- NM_005223
- dbSNP
- rs147763166
- Type
- single nucleotide variant
- Location
- chr16:3657795 (GRCh38)
- Gene constraint
- LOEUF 1.46 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 94.68 · 1 PDB
- Residue 260
- an α-helix
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-ala260 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown