Is DSP p.Arg2548= (c.7644A>T) pathogenic?

DSP p.Arg2548= (c.7644A>T) is classified Likely benign in DSP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-27). Very rare (popmax 0.00333%, amr); Associated with cardiomyopathy.

How common is DSP p.Arg2548= (c.7644A>T) in the general population?

DSP p.Arg2548= (c.7644A>T) is very rare (popmax 0.00333%, amr) (gnomAD).

DSP p.Arg2548=

Q: What condition is associated with DSP p.Arg2548= (c.7644A>T)?

DSP p.Arg2548= (c.7644A>T) is associated with cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.7644A>T · rs886039159 · VCV264442

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

cardiomyopathy

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 -0.41	GERP -3.8, phastCons 0.001
Overall
CADD	1.502	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Arg2548=
Coding: c.7644A>T
MANE Select: NM_004415
dbSNP: rs886039159
Type: single nucleotide variant
Location: chr6:7584906 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2548: 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); the 'binds to telomeres' region; the 'globular 2' 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)

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

Disease context

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

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

Similar variants

DSP p.Arg2548Gly Uncertain significance ★★ same residue
DSP p.Arg2548Pro Uncertain significance ★★ same residue
DSP p.Arg2548Ter Pathogenic ★ same residue
DSP p.Arg2548Gln Conflicting classifications of pathogenicity ★ 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

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-arg2548 (accessed [today's date]).

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