DNASE2 p.Ser168=
c.504G>A · rs140738663 · VCV1673650
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0827%, 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 -0.99 | GERP -2.8 |
| Overall | ||
| CADD | 4.781 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0827%
African / African-American · 62/75,014 alleles
Filtering AF
0.0661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0602%
Overall
0.00421%
68/1,614,012 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0827% | 1,210 |
| Middle Eastern | 0.033% | 3,031 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| Admixed American | 0.00167% | 59,972 |
| European (non-Finnish) | 8.47e-05% | 1,179,988 |
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.Ser168=
- Coding
- c.504G>A
- MANE Select
- NM_001375
- dbSNP
- rs140738663
- Type
- single nucleotide variant
- Location
- chr19:12878677 (GRCh38)
- Gene constraint
- LOEUF 1.195 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
Similar variants
- DNASE2 p.Ser168Leu Uncertain significance ★ ⚠ same residue
- DNASE2 p.Ser168Trp 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
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-ser168 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown