Is DSC2 p.Asp534Val (c.1601A>T) pathogenic?

DSC2 p.Asp534Val (c.1601A>T) is classified Uncertain significance in DSC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-18). AlphaMissense: likely pathogenic (0.8813); Very rare (popmax 6.84e-05%); Associated with Cardiovascular phenotype.

What condition is associated with DSC2 p.Asp534Val (c.1601A>T)?

DSC2 p.Asp534Val (c.1601A>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DSC2 p.Asp534Val (c.1601A>T) in the general population?

DSC2 p.Asp534Val (c.1601A>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DSC2 p.Asp534Val (c.1601A>T)?

AlphaMissense predicts likely pathogenic (score 0.8813) — an in-silico prediction, not a clinical call.

DSC2 p.Asp534Val

c.1601A>T · rs1367187700 · VCV1776186

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8813	likely pathogenic
REVEL	0.639	indeterminate
SaProt	LLR -14.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic
Overall
CADD	29.1	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 6.84e-05%

Overall 6.84e-05% 1/1,461,690 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.Asp534Val
Coding: c.1601A>T
MANE Select: NM_024422
dbSNP: rs1367187700
Type: single nucleotide variant
Location: chr18:31079909 (GRCh38)
Gene constraint: LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.26 · 3 PDB
Residue 534: the cadherin 4 domain

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

Similar variants

DSC2 p.Asp534Gly Uncertain significance ★ ⚠ same residue
DSC2 p.Asp534Asn Uncertain significance ★ same residue
DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
DSC2 c.354+2T>A Likely pathogenic ★★ same condition
DSC2 p.Gln620Ter Pathogenic ★★ same condition
DSC2 p.Tyr221Ter Pathogenic/Likely pathogenic ★★ same condition
DSC2 c.2508+1G>A Uncertain significance ★★ same condition
DSC2 c.355-3G>T Uncertain significance ★★ 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-asp534val (accessed [today's date]).

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