Is TRDN p.Glu142fs (c.423del) pathogenic?

TRDN p.Glu142fs (c.423del) is classified Pathogenic/Likely pathogenic in TRDN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Very rare (popmax 0.00797%, amr); Associated with catecholaminergic polymorphic ventricular tachycardia.

What condition is associated with TRDN p.Glu142fs (c.423del)?

TRDN p.Glu142fs (c.423del) is associated with catecholaminergic polymorphic ventricular tachycardia, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Glu142fs (c.423del) in the general population?

TRDN p.Glu142fs (c.423del) is very rare (popmax 0.00797%, amr) (gnomAD).

TRDN p.Glu142fs

Q: How is Catecholaminergic polymorphic ventricular tachycardia inherited?

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

c.423del · rs757805966 · VCV1074440

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00797%, amr)

Conditions

catecholaminergic polymorphic ventricular tachycardia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 41
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00797% Admixed American · 3/37,638 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00138% 20/1,454,194 alleles · very rare exomes 19/1,302,460 · genomes 1/151,734 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00797%	12,546
Remaining individualsnot grpmax-eligible	0.00356%	28,055
South Asian	0.0015%	66,640
European (non-Finnish)	0.00128%	78,289

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.Glu142fs
Coding: c.423del
MANE Select: NM_006073
dbSNP: rs757805966
Type: Deletion
Location: chr6:123547341 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 142: the 'disordered' region

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

Disease context

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

Also linked: catecholaminergic polymorphic ventricular tachycardia 1

For Catecholaminergic polymorphic ventricular tachycardia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

TRDN p.Glu142Ter Pathogenic ★ same residue
TRDN p.Asp146_Lys147insTer Pathogenic ★★ same condition
TRDN p.Asp18fs Pathogenic ★★ same condition
TRDN p.Glu178fs Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Leu109fs Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Lys147fs Pathogenic ★★ same condition
TRDN p.Val162fs Pathogenic/Likely pathogenic ★★ same condition
TRDN c.1975+4del 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/trdn-p-glu142fs (accessed [today's date]).

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