DSG2 c.1280+287C>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 7.82%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +287 | deep intronic (+287 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -1.8 |
| Non-coding constraint | Z 1.15 | 1 kb window · o/e 0.91 · regional · uncalibrated |
| Overall | ||
| CADD | 0.757 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.82%
Middle Eastern · 23/294 alleles
Filtering AF
5.35%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.8%
Overall
3.6%
5,486/152,278 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 7.82% | 13 |
| Ashkenazi Jewishnot grpmax-eligible | 6.91% | 14 |
| Finnishnot grpmax-eligible | 6.52% | 15 |
| Amishnot grpmax-eligible | 5.04% | 20 |
| European (non-Finnish) | 5% | 20 |
| Remaining individualsnot grpmax-eligible | 4.45% | 22 |
| Admixed American | 3.65% | 27 |
| South Asian | 1.68% | 60 |
| African / African-American | 0.849% | 118 |
| East Asian | 0.0385% | 2,595 |
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
- DSG2
- Coding
- c.1280+287C>A
- MANE Select
- NM_001943
- dbSNP
- rs74699553
- Type
- single nucleotide variant
- Location
- chr18:31531539 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
Similar variants
- DSG2 c.1423+1G>T Likely pathogenic ★★ same type
- DSG2 c.1424-1G>A Likely pathogenic ★★ same type
- DSG2 c.523+1G>T Pathogenic/Likely pathogenic ★★ same type
- DSG2 c.690+1G>A Pathogenic ★★ same type
- DSG2 c.81+1G>T Likely pathogenic ★★ same type
- DSG2 c.829-2A>T Likely pathogenic ★★ same type
- DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same type
- DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ 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/dsg2-c-1280-plus-287c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown