Is DSP p.Cys78Gly (c.232T>G) pathogenic?

DSP p.Cys78Gly (c.232T>G) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-11). AlphaMissense: ambiguous (0.4363); Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Cys78Gly (c.232T>G)?

DSP p.Cys78Gly (c.232T>G) is associated with arrhythmogenic right ventricular dysplasia 8, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Cys78Gly (c.232T>G) in the general population?

DSP p.Cys78Gly (c.232T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSP p.Cys78Gly (c.232T>G)?

AlphaMissense predicts ambiguous (score 0.4363) — an in-silico prediction, not a clinical call.

DSP p.Cys78Gly

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.232T>G · rs1758490063 · VCV1009019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

arrhythmogenic right ventricular dysplasia 8

Computational evidence

Protein change
AlphaMissense	0.4363	ambiguous
REVEL	0.746	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Cys78Gly
Coding: c.232T>G
MANE Select: NM_004415
dbSNP: rs1758490063
Type: single nucleotide variant
Location: chr6:7555779 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 78: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region

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

Disease context

arrhythmogenic right ventricular dysplasia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: arrhythmogenic cardiomyopathy with wooly hair and keratoderma

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSP p.Cys78Phe Uncertain significance ★ ⚠ same residue
DSP p.Cys78= Benign ★ 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

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-cys78gly (accessed [today's date]).

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