Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.97%, 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 0.6 | GERP -1.2, phastCons 0.99 |
| Overall | ||
| CADD | 7.273 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.97%
African / African-American · 1,472/74,856 alleles
Filtering AF
1.88%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.85%
Overall
0.104%
1,682/1,612,474 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.97% | 51 |
| Remaining individualsnot grpmax-eligible | 0.181% | 552 |
| Middle Eastern | 0.149% | 673 |
| Admixed American | 0.0985% | 1,015 |
| South Asian | 0.00661% | 15,123 |
| European (non-Finnish) | 0.00195% | 51,272 |
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
- DSG3
- Protein
- p.Arg227=
- Coding
- c.679C>A
- MANE Select
- NM_001944
- dbSNP
- rs1870642
- Type
- single nucleotide variant
- Location
- chr18:31460006 (GRCh38)
- Gene constraint
- LOEUF 0.862 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.37 · 1 PDB
- Residue 227
- a turn; the cadherin 2 domain
Similar variants
- DSG3 p.Leu856Val Uncertain significance ★★ same type
- DSG3 c.1272-24G>A Benign ★★ same type
- DSG3 c.1412-63T>G Benign ★★ same type
- DSG3 c.1412-92T>C Benign ★★ same type
- DSG3 c.1412-95G>A Benign ★★ same type
- DSG3 c.1637-34C>T Benign ★★ same type
- DSG3 c.1897+60A>G Benign ★★ same type
- DSG3 c.2101+132G>C Benign ★★ 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/dsg3-p-arg227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown