Is TRDN p.Lys542= (c.1626A>G) pathogenic?

TRDN p.Lys542= (c.1626A>G) is classified Likely benign in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-31). Ultra-rare (popmax 0.0173%, mid); Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with TRDN p.Lys542= (c.1626A>G)?

TRDN p.Lys542= (c.1626A>G) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Lys542= (c.1626A>G) in the general population?

TRDN p.Lys542= (c.1626A>G) is ultra-rare (popmax 0.0173%, mid) (gnomAD).

TRDN p.Lys542=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1626A>G · rs1394064564 · VCV1951141

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, mid)

Conditions

catecholaminergic polymorphic ventricular tachycardia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -2.2, phastCons 1
Overall
CADD	9.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% Middle Eastern · 1/5,786 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000333% 5/1,501,122 alleles · ultra-rare exomes 5/1,348,952 · genomes 0/152,170 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0173%	5,786
Remaining individualsnot grpmax-eligible	0.00345%	28,978
European (non-Finnish)	0.000177%	564,051

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: TRDN
Protein: p.Lys542=
Coding: c.1626A>G
MANE Select: NM_006073
dbSNP: rs1394064564
Type: single nucleotide variant
Location: chr6:123273010 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 542: 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 p.Lys542Ter Uncertain significance ★ same residue
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

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-lys542 (accessed [today's date]).

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