DNASE2 p.Phe281=
c.843C>T · rs147756222 · VCV1164634
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.94%, afr)
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 1.7 | GERP 0.27, phastCons 1 |
| Overall | ||
| CADD | 6.326 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.94%
African / African-American · 2,204/75,052 alleles
Filtering AF
2.83%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.79%
Overall
0.154%
2,491/1,614,198 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.94% | 34 |
| Admixed American | 0.2% | 500 |
| Remaining individualsnot grpmax-eligible | 0.171% | 584 |
| Middle Eastern | 0.115% | 866 |
| South Asian | 0.011% | 9,109 |
| European (non-Finnish) | 0.00364% | 27,443 |
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.Phe281=
- Coding
- c.843C>T
- MANE Select
- NM_001375
- dbSNP
- rs147756222
- Type
- single nucleotide variant
- Location
- chr19:12876230 (GRCh38)
- Gene constraint
- LOEUF 1.195 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 281
- 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-phe281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown