DNASE1 p.Ala20=
c.60C>T · VCV4684070
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0767%, 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 -1.9 | GERP -4.2 |
| Overall | ||
| CADD | 4.677 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0767%
Admixed American · 46/60,008 alleles
Filtering AF
0.059%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0528%
Overall
0.00589%
95/1,613,974 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0767% | 1,305 |
| African / African-American | 0.0307% | 3,258 |
| East Asian | 0.0134% | 7,481 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| South Asian | 0.0022% | 45,547 |
| Finnishnot grpmax-eligible | 0.00156% | 63,930 |
| European (non-Finnish) | 0.00102% | 98,335 |
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.Ala20=
- Coding
- c.60C>T
- MANE Select
- NM_005223
- Type
- single nucleotide variant
- Location
- chr16:3655433 (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-ala20 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown