Is TRDN p.Arg93Cys (c.277C>T) pathogenic?

TRDN p.Arg93Cys (c.277C>T) is classified Conflicting classifications of pathogenicity in TRDN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-06). AlphaMissense: likely benign (0.2556); Rare (popmax 0.186%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Arg93Cys (c.277C>T)?

TRDN p.Arg93Cys (c.277C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Arg93Cys (c.277C>T) in the general population?

TRDN p.Arg93Cys (c.277C>T) is rare (popmax 0.186%, afr) (gnomAD).

What do computational predictors say about TRDN p.Arg93Cys (c.277C>T)?

AlphaMissense predicts likely benign (score 0.2556) — an in-silico prediction, not a clinical call.

TRDN p.Arg93Cys

c.277C>T · rs370788759 · VCV415187

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2556 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.186%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2556	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.186% African / African-American · 135/72,712 alleles

Filtering AF 0.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.0117% 182/1,554,868 alleles · rare exomes 99/1,404,404 · genomes 83/150,464 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.186%	539
Middle Eastern	0.0169%	5,926
Remaining individualsnot grpmax-eligible	0.00833%	12,007
Admixed American	0.00761%	13,144
South Asian	0.00736%	13,588
East Asian	0.0047%	21,295
European (non-Finnish)	0.00252%	39,629

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.Arg93Cys
Coding: c.277C>T
MANE Select: NM_006073
dbSNP: rs370788759
Type: single nucleotide variant
Location: chr6:123548568 (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.Arg93Ser Uncertain significance ★★ ⚠ same residue
TRDN p.Arg93His 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

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-arg93cys (accessed [today's date]).

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