Is TRDN p.Ser501= (c.1503C>T) pathogenic?

TRDN p.Ser501= (c.1503C>T) is classified Likely benign in TRDN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-21). Ultra-rare (popmax 0.044%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Ser501= (c.1503C>T)?

TRDN p.Ser501= (c.1503C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Ser501= (c.1503C>T) in the general population?

TRDN p.Ser501= (c.1503C>T) is ultra-rare (popmax 0.044%, sas) (gnomAD).

TRDN p.Ser501=

c.1503C>T · rs758349373 · VCV2960275

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.99	GERP -3.3, phastCons 1
Overall
CADD	1.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.044% South Asian · 40/90,926 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.00267% 43/1,609,642 alleles · ultra-rare exomes 42/1,458,052 · genomes 1/151,590 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.044%	2,273
Middle Eastern	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.00161%	62,258
European (non-Finnish)	8.49e-05%	1,177,390

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.Ser501=
Coding: c.1503C>T
MANE Select: NM_006073
dbSNP: rs758349373
Type: single nucleotide variant
Location: chr6:123316464 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 501: 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.Ser501Thr 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-ser501 (accessed [today's date]).

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