DSP p.Ser2831=
c.8493G>A · rs397516969 · VCV227346
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00337%, amr)
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 -20 | GERP -3.5 |
| Overall | ||
| CADD | 0.002 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00337%
Admixed American · 2/59,276 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000832%
Overall
0.00143%
23/1,609,454 alleles · very rare
exomes 22/1,457,364 · genomes 1/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00337% | 29,638 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,115 |
| European (non-Finnish) | 0.00161% | 61,979 |
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.Ser2831=
- Coding
- c.8493G>A
- MANE Select
- NM_004415
- dbSNP
- rs397516969
- Type
- single nucleotide variant
- Location
- chr6:7585755 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2831
- 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); a UniProt-annotated variant site (in ebla; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance); the 'binds to telomeres' region; the 'globular 2' region; the 'disordered' region; the '6 x 4 aa tandem repeats of g-s-r-[sr]' 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.Ser2831Leu 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-ser2831 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown