Is TRDN p.Val162fs (c.483del) pathogenic?

TRDN p.Val162fs (c.483del) is classified Pathogenic/Likely pathogenic in TRDN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-29). Very rare (popmax 0.000322%, nfe); Associated with catecholaminergic polymorphic ventricular tachycardia 5.

What condition is associated with TRDN p.Val162fs (c.483del)?

TRDN p.Val162fs (c.483del) is associated with catecholaminergic polymorphic ventricular tachycardia 5, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Val162fs (c.483del) in the general population?

TRDN p.Val162fs (c.483del) is very rare (popmax 0.000322%, nfe) (gnomAD).

TRDN p.Val162fs

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.483del · rs1780193710 · VCV2732852

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000322%, nfe)

Conditions

catecholaminergic polymorphic ventricular tachycardia 5

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 5 of 41
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 0.91, phastCons 1
Overall
CADD	28.4	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 0.000322% European (non-Finnish) · 3/931,066 alleles

Filtering AF 8.6e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.4e-05%

Overall 0.000321% 4/1,244,948 alleles · very rare exomes 4/1,093,408 · genomes 0/151,540 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00213%	46,968
European (non-Finnish)grpmax	0.000322%	310,356

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.Val162fs
Coding: c.483del
MANE Select: NM_006073
dbSNP: rs1780193710
Type: Deletion
Location: chr6:123530507 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 162: the 'disordered' region

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

Disease context

catecholaminergic polymorphic ventricular tachycardia 5 — 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.Val162= Likely benign ★ same residue
TRDN p.Asp146_Lys147insTer Pathogenic ★★ same condition
TRDN p.Asp18fs Pathogenic ★★ same condition
TRDN p.Glu142fs Pathogenic/Likely 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 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-val162fs (accessed [today's date]).

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