DSG2 p.Thr695=
c.2085G>A · rs554396523 · VCV466334
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Conditions
4
Cardiovascular phenotype
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 -6.6 | |
| Overall | ||
| CADD | 0.793 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,060 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00291%
47/1,614,132 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,020 |
| African / African-American | 0.008% | 12,501 |
| South Asian | 0.00439% | 22,769 |
| Admixed American | 0.00333% | 30,009 |
| European (non-Finnish) | 0.00263% | 38,065 |
| East Asian | 0.00223% | 44,872 |
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
- Protein
- p.Thr695=
- Coding
- c.2085G>A
- MANE Select
- NM_001943
- dbSNP
- rs554396523
- Type
- single nucleotide variant
- Location
- chr18:31542603 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 695
- a UniProt-annotated variant site (in arvd10; uncertain significance; evidence of residual myocardium, fibrous tissue, fatty tissue, dysmetric and dysmorphic nuclei and prominent cytoplasmic vacuolization; decreases the number of desmosomes at intercalated disks also increases desmosome gap; smaller intercellular gaps, with repeating couplings, abnormally located desmosomes and pale internal plaques)
Similar variants
- DSG2 p.Thr695Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- DSG2 c.1423+1G>T Likely pathogenic ★★ same condition
- DSG2 c.1424-1G>A Likely pathogenic ★★ same condition
- DSG2 c.523+1G>T Pathogenic/Likely pathogenic ★★ same condition
- DSG2 c.690+1G>A Pathogenic ★★ same condition
- DSG2 c.81+1G>T Likely pathogenic ★★ same condition
- DSG2 c.829-2A>T Likely pathogenic ★★ same condition
- DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
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-p-thr695 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown