DNASE2 p.Ser145=
c.435C>T · rs2293682 · VCV1168081
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 66.4%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.55 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -2.8, phastCons 0.98 |
| Overall | ||
| CADD | 5.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
66.4%
East Asian · 29,776/44,844 alleles
Filtering AF
65.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 65.5%
Overall
26.6%
429,671/1,613,616 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 66.4% | 2 |
| South Asian | 41.8% | 2 |
| Finnishnot grpmax-eligible | 33.2% | 3 |
| Admixed American | 32% | 3 |
| Remaining individualsnot grpmax-eligible | 27.7% | 4 |
| African / African-American | 25.9% | 4 |
| European (non-Finnish) | 23.5% | 4 |
| Middle Eastern | 20.7% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 20.5% | 5 |
| Amishnot grpmax-eligible | 19% | 5 |
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
- DNASE2
- Protein
- p.Ser145=
- Coding
- c.435C>T
- MANE Select
- NM_001375
- dbSNP
- rs2293682
- Type
- single nucleotide variant
- Location
- chr19:12878746 (GRCh38)
- Gene constraint
- LOEUF 1.195 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 145
- a disulfide bond
Similar variants
- DNASE2 p.Ser145Ile Uncertain significance ★ same residue
- DNASE2 c.709+4A>T Uncertain significance ★★ same type
- DNASE2 p.Ala332Asp Uncertain significance ★★ ⚠ same type
- DNASE2 p.Arg321Trp Uncertain significance ★★ ⚠ same type
- DNASE2 p.Asn69Ser Uncertain significance ★★ ⚠ same type
- DNASE2 p.Cys159Trp Uncertain significance ★★ ⚠ same type
- DNASE2 p.Glu43Gly Uncertain significance ★★ ⚠ same type
- DNASE2 p.Gly241Ser 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/dnase2-p-ser145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown