DNASE1L3 p.Ile243=
c.729C>T · rs76440799 · VCV1957480
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
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 -2.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,882 alleles
Filtering AF
0.00434%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00112%
18/1,613,706 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,976 |
| Admixed American | 0.00333% | 29,995 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| African / African-American | 0.00134% | 74,894 |
| South Asian | 0.0011% | 91,046 |
| European (non-Finnish) | 0.000678% | 147,474 |
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
- DNASE1L3
- Protein
- p.Ile243=
- Coding
- c.729C>T
- MANE Select
- NM_004944
- dbSNP
- rs76440799
- Type
- single nucleotide variant
- Location
- chr3:58193415 (GRCh38)
- Gene constraint
- LOEUF 1.122 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.08 · 1 PDB
- Residue 243
- a UniProt-annotated variant site (in); an α-helix
Similar variants
- DNASE1L3 p.Ile243Met Uncertain significance ★★ ⚠ same residue
- DNASE1L3 c.802-20C>G Uncertain significance ★★ same type
- DNASE1L3 p.Ala18Thr Uncertain significance ★★ ⚠ same type
- DNASE1L3 p.Ala201Thr Uncertain significance ★★ ⚠ same type
- DNASE1L3 p.Ala268Gly Uncertain significance ★★ ⚠ same type
- DNASE1L3 p.Arg22Lys Uncertain significance ★★ ⚠ same type
- DNASE1L3 p.Arg285Lys Uncertain significance ★★ ⚠ same type
- DNASE1L3 p.Arg304Cys 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/dnase1l3-p-ile243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown