DSP p.Ala1584=
c.4752G>A · rs201213622 · VCV264550
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0401%, eas)
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 -1.2 | GERP -3.8 |
| Overall | ||
| CADD | 6.889 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0401%
East Asian · 18/44,878 alleles
Filtering AF
0.0259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0214%
Overall
0.00353%
57/1,614,120 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0401% | 2,493 |
| Admixed American | 0.0117% | 8,575 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,417 |
| Finnishnot grpmax-eligible | 0.00469% | 21,329 |
| African / African-American | 0.004% | 25,014 |
| European (non-Finnish) | 0.00161% | 62,106 |
| South Asian | 0.0011% | 91,082 |
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.Ala1584=
- Coding
- c.4752G>A
- MANE Select
- NM_004415
- dbSNP
- rs201213622
- Type
- single nucleotide variant
- Location
- chr6:7580942 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1584
- 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)
Similar variants
- DSP p.Ala1584Val Uncertain significance ★★ ⚠ same residue
- DSP p.Ala1584Thr Likely benign ★★ same residue
- DSP p.Ala1584Gly Uncertain significance ★ ⚠ same residue
- DSP p.Ala1584Pro Uncertain significance ★ ⚠ same residue
- DSP p.Ala1584Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- DSP p.Ala1584fs Pathogenic ★ same residue
- DSP c.1141-2A>T Likely pathogenic ★★ same condition
- DSP c.1266+2T>C 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-ala1584 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown