Is TRDN p.Thr37Ser (c.109A>T) pathogenic?

TRDN p.Thr37Ser (c.109A>T) is classified Uncertain significance in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-28). AlphaMissense: likely benign (0.3351); Absent from gnomAD v4.1; Associated with catecholaminergic polymorphic ventricular tachycardia.

What condition is associated with TRDN p.Thr37Ser (c.109A>T)?

TRDN p.Thr37Ser (c.109A>T) is associated with catecholaminergic polymorphic ventricular tachycardia (ClinVar).

How common is TRDN p.Thr37Ser (c.109A>T) in the general population?

TRDN p.Thr37Ser (c.109A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRDN p.Thr37Ser (c.109A>T)?

AlphaMissense predicts likely benign (score 0.3351) — an in-silico prediction, not a clinical call.

TRDN p.Thr37Ser

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.109A>T · rs1554258810 · VCV532344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3351 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

catecholaminergic polymorphic ventricular tachycardia

Computational evidence

Protein change
AlphaMissense	0.3351	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRDN
Protein: p.Thr37Ser
Coding: c.109A>T
MANE Select: NM_006073
dbSNP: rs1554258810
Type: single nucleotide variant
Location: chr6:123571046 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65

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

Disease context

catecholaminergic polymorphic ventricular tachycardia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Thr37Ile Uncertain significance ★★ ⚠ same residue
TRDN p.Thr37Arg Uncertain significance ★ ⚠ same residue
TRDN p.Thr37= Likely benign ★ same residue
TRDN p.Gln205Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN c.1975+5G>T Uncertain significance ★★ same condition
TRDN p.Ala574Thr Uncertain significance ★ ⚠ same condition
TRDN p.Glu340Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
TRDN p.Ser622Gly 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-thr37ser (accessed [today's date]).

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