Is DSC2 p.Gly77Val (c.230G>T) pathogenic?

DSC2 p.Gly77Val (c.230G>T) is classified Uncertain significance in DSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-05-16). AlphaMissense: likely pathogenic (0.8992); Very rare (popmax 0.000932%, nfe); Associated with familial isolated arrhythmogenic right ventricular dysplasia.

What condition is associated with DSC2 p.Gly77Val (c.230G>T)?

DSC2 p.Gly77Val (c.230G>T) is associated with familial isolated arrhythmogenic right ventricular dysplasia, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Gly77Val (c.230G>T) in the general population?

DSC2 p.Gly77Val (c.230G>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about DSC2 p.Gly77Val (c.230G>T)?

AlphaMissense predicts likely pathogenic (score 0.8992) — an in-silico prediction, not a clinical call.

DSC2 p.Gly77Val

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.230G>T · rs761544006 · VCV918362

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial isolated arrhythmogenic right ventricular dysplasia

Computational evidence

Protein change
AlphaMissense	0.8992	likely pathogenic
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -15.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,834 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000753% 11/1,461,512 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: DSC2
Protein: p.Gly77Val
Coding: c.230G>T
MANE Select: NM_024422
dbSNP: rs761544006
Type: single nucleotide variant
Location: chr18:31092225 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB

Full DSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 11

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSC2 p.Gly77Asp Uncertain significance ★★ ⚠ same residue
DSC2 p.Gly77Ser Uncertain significance ★ ⚠ same residue
DSC2 p.Gly77= Likely benign ★ same residue
DSC2 p.Gly77Ala Uncertain significance ★ ⚠ same residue
DSC2 c.1664-1G>A Likely pathogenic ★★ same condition
DSC2 c.354+2T>A Likely pathogenic ★★ same condition
DSC2 c.355-1G>A Likely pathogenic ★★ same condition
DSC2 p.Gln554Ter 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/dsc2-p-gly77val (accessed [today's date]).

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