Is DSC2 p.Ile24Val (c.70A>G) pathogenic?

DSC2 p.Ile24Val (c.70A>G) is classified Uncertain significance in DSC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-23). AlphaMissense: likely benign (0.0673); Very rare (popmax 0.0017%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Ile24Val (c.70A>G)?

DSC2 p.Ile24Val (c.70A>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 11 (ClinVar).

How common is DSC2 p.Ile24Val (c.70A>G) in the general population?

DSC2 p.Ile24Val (c.70A>G) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about DSC2 p.Ile24Val (c.70A>G)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

DSC2 p.Ile24Val

c.70A>G · rs1228372400 · VCV1332353

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -4.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.58, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic
Overall
CADD	8.152	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0017% Admixed American · 1/58,882 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000211% 3/1,420,976 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,882
European (non-Finnish)	0.000173%	577,194

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.Ile24Val
Coding: c.70A>G
MANE Select: NM_024422
dbSNP: rs1228372400
Type: single nucleotide variant
Location: chr18:31093643 (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

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

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 11

Similar variants

DSC2 p.Ile24= Likely benign ★★ same residue
DSC2 p.Ile24Asn Uncertain significance ★ ⚠ same residue
DSC2 p.Ile24Phe Uncertain significance ★ ⚠ same residue
DSC2 p.Ile24Leu Uncertain significance ★ ⚠ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
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

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-ile24val (accessed [today's date]).

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