DSP p.Ala385=
c.1155G>A · rs140488069 · VCV378907
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 -2.8 | GERP -3.9 |
| Overall | ||
| CADD | 5.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0141% | 7,104 |
| East Asiangrpmax | 0.0111% | 8,971 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| European (non-Finnish) | 0.00687% | 14,566 |
| Admixed American | 0.00333% | 29,994 |
| South Asian | 0.00329% | 30,357 |
| African / African-American | 0.00267% | 37,482 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- DSP
- Protein
- p.Ala385=
- Coding
- c.1155G>A
- MANE Select
- NM_004415
- dbSNP
- rs140488069
- Type
- single nucleotide variant
- Location
- chr6:7567795 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 385
- an α-helix; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8; likely pathogenic; results in an unstable protein that forms perinuclear aggregates); a UniProt-annotated variant site (in arvd8 and dcwhkta; uncertain significance)
Disease context
arrhythmogenic right ventricular dysplasia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: cardiomyopathyarrhythmogenic cardiomyopathy with wooly hair and keratodermalethal acantholytic epidermolysis bullosakeratosis palmoplantaris striata 2cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesiswoolly hair-skin fragility syndrome
For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- No data available
Similar variants
- DSP p.Ala385Val Likely benign ★★ same residue
- DSP c.1141-2A>T Likely pathogenic ★★ same condition
- DSP c.1266+2T>C Likely pathogenic ★★ same condition
- DSP c.1574+1G>A Likely pathogenic ★★ same condition
- DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DSP c.2297+1G>A Likely pathogenic ★★ same condition
- DSP c.2298-1G>C Likely pathogenic ★★ same condition
- DSP c.2298-2A>C 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/dsp-p-ala385 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown