DNASE2 p.Cys299=
c.897C>T · rs752412117 · VCV1672006
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.116%, mid)
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>T here scores Δ0.58 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.64 | GERP -2.8, phastCons 0.92 |
| Overall | ||
| CADD | 10.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.116%
Middle Eastern · 7/6,060 alleles
Filtering AF
0.0542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0384%
Overall
0.00644%
104/1,614,206 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.116% | 866 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,209 |
| South Asian | 0.0143% | 7,006 |
| European (non-Finnish) | 0.00568% | 17,613 |
| Admixed American | 0.00333% | 30,007 |
| African / African-American | 0.00266% | 37,530 |
| East Asian | 0.00223% | 44,878 |
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.Cys299=
- Coding
- c.897C>T
- MANE Select
- NM_001375
- dbSNP
- rs752412117
- Type
- single nucleotide variant
- Location
- chr19:12876176 (GRCh38)
- Gene constraint
- LOEUF 1.195 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 299
- a disulfide bond
Similar variants
- 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
- DNASE2 p.Gly286Ser 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-cys299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown