Is TRDN p.Glu571Asp (c.1713A>C) pathogenic?

TRDN p.Glu571Asp (c.1713A>C) is classified Conflicting classifications of pathogenicity in TRDN (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.1624); Rare (popmax 0.451%, afr); Associated with catecholaminergic polymorphic ventricular tachycardia 5.

What condition is associated with TRDN p.Glu571Asp (c.1713A>C)?

TRDN p.Glu571Asp (c.1713A>C) is associated with catecholaminergic polymorphic ventricular tachycardia 5, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Glu571Asp (c.1713A>C) in the general population?

TRDN p.Glu571Asp (c.1713A>C) is rare (popmax 0.451%, afr) (gnomAD).

What do computational predictors say about TRDN p.Glu571Asp (c.1713A>C)?

AlphaMissense predicts likely benign (score 0.1624) — an in-silico prediction, not a clinical call.

TRDN p.Glu571Asp

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.1713A>C · rs201115952 · VCV415185

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1624 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.451%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

catecholaminergic polymorphic ventricular tachycardia 5

Computational evidence

Protein change
AlphaMissense	0.1624	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	21.0	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 0.451% African / African-American · 326/72,260 alleles

Filtering AF 0.411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.395%

Overall 0.0228% 350/1,534,802 alleles · rare exomes 154/1,382,710 · genomes 196/152,092 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.451%	222
Remaining individualsnot grpmax-eligible	0.0218%	4,578
Middle Eastern	0.0169%	5,902
Admixed American	0.0166%	6,025
South Asian	0.00123%	81,480
European (non-Finnish)	8.77e-05%	1,140,547

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.Glu571Asp
Coding: c.1713A>C
MANE Select: NM_006073
dbSNP: rs201115952
Type: single nucleotide variant
Location: chr6:123271146 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 571: the 'disordered' region

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

Disease context

catecholaminergic polymorphic ventricular tachycardia 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: catecholaminergic polymorphic ventricular tachycardia 1

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.Glu571Lys 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
TRDN p.Lys177Ter 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-glu571asp (accessed [today's date]).

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