Is TRDN p.Asp125= (c.375C>T) pathogenic?

TRDN p.Asp125= (c.375C>T) is classified Likely benign in TRDN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.0478%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Asp125= (c.375C>T)?

TRDN p.Asp125= (c.375C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Asp125= (c.375C>T) in the general population?

TRDN p.Asp125= (c.375C>T) is ultra-rare (popmax 0.0478%, sas) (gnomAD).

TRDN p.Asp125=

c.375C>T · rs377440434 · VCV264376

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0478%, 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	all four deltas below 0.2 · G>C here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -3.1
Overall
CADD	0.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0478% South Asian · 39/81,558 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.033% 515/1,562,774 alleles · ultra-rare exomes 483/1,411,288 · genomes 32/151,486 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0478%	2,091
European (non-Finnish)	0.0376%	2,657
Admixed American	0.0306%	3,268
Remaining individualsnot grpmax-eligible	0.0249%	4,015
Middle Eastern	0.017%	5,874
African / African-American	0.00825%	12,128
East Asian	0.00458%	21,842
Finnishnot grpmax-eligible	0.00162%	61,858

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.Asp125=
Coding: c.375C>T
MANE Select: NM_006073
dbSNP: rs377440434
Type: single nucleotide variant
Location: chr6:123548470 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 125: 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 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
TRDN p.Met1Thr 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-asp125 (accessed [today's date]).

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