Is DSP p.2858YS[1] (c.8577_8588del) pathogenic?

DSP p.2858YS[1] (c.85778588del) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-04). Very rare (popmax 0.004%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.2858YS[1] (c.8577_8588del)?

DSP p.2858YS[1] (c.8577_8588del) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.2858YS[1] (c.8577_8588del) in the general population?

DSP p.2858YS[1] (c.8577_8588del) is very rare (popmax 0.004%, afr) (gnomAD).

DSP p.2858YS[1]

c.8577_8588del · rs2113705755 · VCV1346584

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,972 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000205% 3/1,461,102 alleles · very rare

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.2858YS[1]
Coding: c.8577_8588del
MANE Select: NM_004415
dbSNP: rs2113705755
Type: Deletion
Location: chr6:7585830 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full DSP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

Similar variants

DSP c.2131-3_2131del Likely pathogenic ★★ same condition
DSP p.Ala2092fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1113fs Pathogenic ★★ same condition
DSP p.Arg1173fs Pathogenic ★★ same condition
DSP p.Arg1506fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asn1346fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asn257fs Pathogenic ★★ same condition
DSP p.Asp1120fs 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-2858ys-1 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown