Is TRDN p.Glu3Asp (c.9G>C) pathogenic?

TRDN p.Glu3Asp (c.9G>C) is classified Uncertain significance in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.6782); Absent from gnomAD v4.1; Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with TRDN p.Glu3Asp (c.9G>C)?

TRDN p.Glu3Asp (c.9G>C) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Glu3Asp (c.9G>C) in the general population?

TRDN p.Glu3Asp (c.9G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRDN p.Glu3Asp (c.9G>C)?

AlphaMissense predicts likely pathogenic (score 0.6782) — an in-silico prediction, not a clinical call.

TRDN p.Glu3Asp

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.9G>C · rs1185669572 · VCV1473722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

catecholaminergic polymorphic ventricular tachycardia 1

Computational evidence

Protein change
AlphaMissense	0.6782	likely pathogenic · top 9% in TRDN
REVEL	0.214	benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	22.5	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: TRDN
Protein: p.Glu3Asp
Coding: c.9G>C
MANE Select: NM_006073
dbSNP: rs1185669572
Type: single nucleotide variant
Location: chr6:123636767 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 3: the 'disordered' region

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

Disease context

catecholaminergic polymorphic ventricular tachycardia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

TRDN c.22+1G>T Pathogenic ★★ same condition
TRDN c.22+29A>G Pathogenic ★★ same condition
TRDN c.391+1G>A Likely pathogenic ★★ same condition
TRDN p.Gln205Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Glu168Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Glu181Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Lys177Ter Pathogenic ★★ same condition
TRDN p.Met1Thr 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/trdn-p-glu3asp (accessed [today's date]).

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