Is TRDN p.Lys598fs (c.1794del) pathogenic?

TRDN p.Lys598fs (c.1794del) is classified Uncertain significance in TRDN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-05). Very rare (popmax 0.00267%, eas); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Lys598fs (c.1794del)?

TRDN p.Lys598fs (c.1794del) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Lys598fs (c.1794del) in the general population?

TRDN p.Lys598fs (c.1794del) is very rare (popmax 0.00267%, eas) (gnomAD).

TRDN p.Lys598fs

c.1794del · rs1412913007 · VCV1400526

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, eas)

Conditions

Cardiovascular phenotype

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 33 of 41
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.68	GERP -0.63, phastCons 0.99
Overall
CADD	25.1	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 0.00267% East Asian · 1/37,510 alleles

Filtering AF 0.000274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000176%

Overall 0.000563% 8/1,420,110 alleles · very rare exomes 6/1,268,714 · genomes 2/151,396 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00267%	37,510
European (non-Finnish)	0.000659%	151,705

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.Lys598fs
Coding: c.1794del
MANE Select: NM_006073
dbSNP: rs1412913007
Type: Deletion
Location: chr6:123265328 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 598: the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: catecholaminergic polymorphic ventricular tachycardia 1

Similar variants

TRDN p.Lys598= 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 p.Val162fs Pathogenic/Likely 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-lys598fs (accessed [today's date]).

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