Is TRDN p.Asp18fs (c.53_56del) pathogenic?

TRDN p.Asp18fs (c.5356del) is classified Pathogenic in TRDN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-17). Ultra-rare (popmax 0.0788%, afr); Associated with TRDN-related disorder.

How common is TRDN p.Asp18fs (c.53_56del) in the general population?

TRDN p.Asp18fs (c.53_56del) is ultra-rare (popmax 0.0788%, afr) (gnomAD).

TRDN p.Asp18fs

Q: What condition is associated with TRDN p.Asp18fs (c.53_56del)?

TRDN p.Asp18fs (c.53_56del) is associated with TRDN-related disorder, catecholaminergic polymorphic ventricular tachycardia 1, catecholaminergic polymorphic ventricular tachycardia 5 (ClinVar).

c.53_56del · rs768049331 · VCV66015

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0788%, afr)

Conditions

TRDN-related disorder

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 2 of 41
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 1.2, phastCons 1
Overall
CADD	34.0	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 0.0788% African / African-American · 59/74,912 alleles

Filtering AF 0.0626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0568%

Overall 0.0039% 63/1,613,766 alleles · ultra-rare exomes 33/1,461,628 · genomes 30/152,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0788%	1,270
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	0.00017%	589,918

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.Asp18fs
Coding: c.53_56del
MANE Select: NM_006073
dbSNP: rs768049331
Type: Deletion
Location: chr6:123571099 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 18: the 'disordered' region

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

Disease context

TRDN-related disorder

Also linked: catecholaminergic polymorphic ventricular tachycardia 1 catecholaminergic polymorphic ventricular tachycardia 5

Similar variants

TRDN p.Asp18His Uncertain significance ★★ ⚠ same residue
TRDN p.Asp146_Lys147insTer 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
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-asp18fs (accessed [today's date]).

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