Is TRDN p.Arg271Ter (c.811C>T) pathogenic?

TRDN p.Arg271Ter (c.811C>T) is classified Uncertain significance in TRDN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-08-31). Ultra-rare (popmax 0.0336%, mid); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Arg271Ter (c.811C>T)?

TRDN p.Arg271Ter (c.811C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Arg271Ter (c.811C>T) in the general population?

TRDN p.Arg271Ter (c.811C>T) is ultra-rare (popmax 0.0336%, mid) (gnomAD).

TRDN p.Arg271Ter

c.811C>T · rs1201954479 · VCV936559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0336%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 41
Splicing
SpliceAI	Δ0.42	acceptor loss · deltas
Pangolin	Δ0.65	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Overall
CADD	50.0	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 0.0336% Middle Eastern · 2/5,956 alleles

Filtering AF 0.00591% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00103% 16/1,554,170 alleles · ultra-rare exomes 15/1,402,172 · genomes 1/151,998 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0336%	2,978
Remaining individualsnot grpmax-eligible	0.00333%	30,013
Finnishnot grpmax-eligible	0.00163%	61,506
European (non-Finnish)	0.000956%	104,657

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.Arg271Ter
Coding: c.811C>T
MANE Select: NM_006073
dbSNP: rs1201954479
Type: single nucleotide variant
Location: chr6:123497235 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: catecholaminergic polymorphic ventricular tachycardia 1

Similar variants

TRDN p.Arg271Gln Uncertain significance ★★ ⚠ same residue
TRDN p.Arg271Pro 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-arg271ter (accessed [today's date]).

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