Is TRDN p.Thr569= (c.1707A>G) pathogenic?

TRDN p.Thr569= (c.1707A>G) is classified Likely benign in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). Very rare (popmax 0.00158%, nfe); Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with TRDN p.Thr569= (c.1707A>G)?

TRDN p.Thr569= (c.1707A>G) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Thr569= (c.1707A>G) in the general population?

TRDN p.Thr569= (c.1707A>G) is very rare (popmax 0.00158%, nfe) (gnomAD).

TRDN p.Thr569=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1707A>G · VCV3718942

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00158%, nfe)

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	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.81	GERP -2
Overall
CADD	10.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00158% European (non-Finnish) · 18/1,142,208 alleles

Filtering AF 0.000985% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000813%

Overall 0.0013% 20/1,536,800 alleles · very rare exomes 19/1,384,836 · genomes 1/151,964 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00168%	59,562
European (non-Finnish)grpmax	0.00158%	63,456
South Asian	0.00123%	81,536

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr569=
Coding: c.1707A>G
MANE Select: NM_006073
Type: single nucleotide variant
Location: chr6:123271152 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 569: 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.Thr569Ile 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-thr569 (accessed [today's date]).

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