Is DSP p.Arg315= (c.945C>T) pathogenic?

DSP p.Arg315= (c.945C>T) is classified Likely benign in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-21). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

How common is DSP p.Arg315= (c.945C>T) in the general population?

DSP p.Arg315= (c.945C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

DSP p.Arg315=

Q: What condition is associated with DSP p.Arg315= (c.945C>T)?

DSP p.Arg315= (c.945C>T) is associated with Cardiovascular phenotype, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.945C>T · rs2533876128 · VCV2587398

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -3.3, phastCons 0.094
Overall
CADD	9.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,996 alleles

Overall 0.000124% 2/1,612,814 alleles · very rare exomes 2/1,460,582 · genomes 0/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,996
European (non-Finnish)	8.48e-05%	1,179,390

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.Arg315=
Coding: c.945C>T
MANE Select: NM_004415
dbSNP: rs2533876128
Type: single nucleotide variant
Location: chr6:7566382 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 315: an α-helix; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the 'interaction with pkp1' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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)

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

Similar variants

DSP p.Arg315Pro Uncertain significance ★★ same residue
DSP p.Arg315Cys Conflicting classifications of pathogenicity ★ same residue
DSP p.Arg315His Conflicting classifications of pathogenicity ★ same residue
DSP p.Arg315Leu Conflicting classifications of pathogenicity ★ same residue
DSP p.Arg315fs Pathogenic ★ same residue
DSP p.Arg315Gln Uncertain significance ★ 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-arg315 (accessed [today's date]).

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