DSG1 p.Pro602=
c.1806A>G · rs760394187 · VCV1160990
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00686%, nfe)
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 -1.7 | GERP -3.8 |
| Overall | ||
| CADD | 1.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00686%
European (non-Finnish) · 81/1,180,028 alleles
Filtering AF
0.00563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00508%
82/1,614,022 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00686% | 14,568 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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
- DSG1
- Protein
- p.Pro602=
- Coding
- c.1806A>G
- MANE Select
- NM_001942
- dbSNP
- rs760394187
- Type
- single nucleotide variant
- Location
- chr18:31343568 (GRCh38)
- Gene constraint
- LOEUF 0.455 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.93
- Residue 602
- a UniProt-annotated variant site (in ppks1; uncertain significance; reduces expression of krt10 in keratinocytes); a UniProt-annotated variant site (in ppks1; uncertain significance; reduces protein expression, expression of krt10 and loricrin and increases phosphorylated erk in keratinocytes)
Similar variants
- DSG1 p.Pro602Thr Uncertain significance ★ ⚠ same residue
- DSG1 p.Arg128Ter Pathogenic ★★ same type
- DSG1 p.Arg144Ter Pathogenic ★★ same type
- DSG1 p.Arg219Ter Pathogenic ★★ same type
- DSG1 p.Arg242Ter Pathogenic ★★ same type
- DSG1 p.Arg26Ter Pathogenic ★★ same type
- DSG1 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same type
- DSG1 p.Arg887Ter 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/dsg1-p-pro602 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown