Is TRDN p.Arg271Pro (c.812G>C) pathogenic?

TRDN p.Arg271Pro (c.812G>C) is classified Uncertain significance in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). AlphaMissense: likely pathogenic (0.9945); Very rare (popmax 0.000348%, nfe); Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with TRDN p.Arg271Pro (c.812G>C)?

TRDN p.Arg271Pro (c.812G>C) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Arg271Pro (c.812G>C) in the general population?

TRDN p.Arg271Pro (c.812G>C) is very rare (popmax 0.000348%, nfe) (gnomAD).

What do computational predictors say about TRDN p.Arg271Pro (c.812G>C)?

AlphaMissense predicts likely pathogenic (score 0.9945) — an in-silico prediction, not a clinical call.

TRDN p.Arg271Pro

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.812G>C · rs772783444 · VCV2047820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9945 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000348%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

catecholaminergic polymorphic ventricular tachycardia 1

Computational evidence

Protein change
AlphaMissense	0.9945	likely pathogenic · top 1% in TRDN
REVEL	0.364	indeterminate
SaProt	LLR -13.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.29	donor loss · deltas
Pangolin	Δ0.36	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.000348% European (non-Finnish) · 4/1,151,060 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000257% 4/1,553,814 alleles · very rare exomes 3/1,401,804 · genomes 1/152,010 · joint denominator

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.Arg271Pro
Coding: c.812G>C
MANE Select: NM_006073
dbSNP: rs772783444
Type: single nucleotide variant
Location: chr6:123497234 (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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

TRDN p.Arg271Gln Uncertain significance ★★ ⚠ same residue
TRDN p.Arg271Ter Uncertain significance ★★ same residue
TRDN p.Glu271Lys Likely benign ★ 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

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-arg271pro (accessed [today's date]).

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