DSP p.Ser1623Pro
c.4867T>C · rs749679496 · VCV925427
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8245 | likely pathogenic |
|---|---|---|
| REVEL | 0.383 | indeterminate |
| SaProt | — | not scored · why |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP 0.51, phastCons 0.97 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic |
| Overall | ||
| CADD | 20.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish)grpmax | 0.00136% | 73,750 |
Remaining individuals 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.Ser1623Pro
- Coding
- c.4867T>C
- MANE Select
- NM_004415
- dbSNP
- rs749679496
- Type
- single nucleotide variant
- Location
- chr6:7581057 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1623
- a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); the 'central fibrous rod domain' region; the 'binds to telomeres' region; 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); a UniProt-annotated variant site (in arvd8)
Disease context
arrhythmogenic cardiomyopathy with wooly hair and keratoderma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: cardiomyopathyarrhythmogenic right ventricular dysplasia 8lethal acantholytic epidermolysis bullosakeratosis palmoplantaris striata 2cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis
For Carvajal syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- Childhood, Infancy, Neonatal
Similar variants
- DSP p.Ser1623Cys Uncertain significance ★★ ⚠ 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-ser1623pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown