DNASE2 p.Pro138=
c.414G>A · rs750747420 · VCV1372419
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.42 | GERP -2.6 |
| Overall | ||
| CADD | 5.176 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,948 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00174%
28/1,613,816 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,974 |
| European (non-Finnish) | 0.00203% | 49,166 |
| African / African-American | 0.00134% | 74,858 |
| South Asian | 0.0011% | 91,060 |
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.Pro138=
- Coding
- c.414G>A
- MANE Select
- NM_001375
- dbSNP
- rs750747420
- Type
- single nucleotide variant
- Location
- chr19:12878767 (GRCh38)
- Gene constraint
- LOEUF 1.195 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 138
- a disulfide bond
Similar variants
- DNASE2 p.Pro138Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown