Is TRDN p.Lys531= (c.1593A>G) pathogenic?

TRDN p.Lys531= (c.1593A>G) is classified Conflicting classifications of pathogenicity in TRDN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00402%, afr); Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with TRDN p.Lys531= (c.1593A>G)?

TRDN p.Lys531= (c.1593A>G) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Lys531= (c.1593A>G) in the general population?

TRDN p.Lys531= (c.1593A>G) is very rare (popmax 0.00402%, afr) (gnomAD).

TRDN p.Lys531=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1593A>G · rs769926882 · VCV513043

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Conditions

catecholaminergic polymorphic ventricular tachycardia 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss, 25 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.7	GERP 0.64, phastCons 0.57
Overall
CADD	1.673	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% African / African-American · 3/74,702 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000746% 12/1,608,060 alleles · very rare exomes 10/1,456,024 · genomes 2/152,036 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,901
Remaining individualsnot grpmax-eligible	0.00161%	62,170
European (non-Finnish)	0.00068%	147,106

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.Lys531=
Coding: c.1593A>G
MANE Select: NM_006073
dbSNP: rs769926882
Type: single nucleotide variant
Location: chr6:123274645 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 531: 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-lys531 (accessed [today's date]).

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