Is TRDN p.Ala95Val (c.284C>T) pathogenic?

TRDN p.Ala95Val (c.284C>T) is classified Uncertain significance in TRDN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-10-21). AlphaMissense: ambiguous (0.3532); Very rare (popmax 0.0036%, sas); Associated with catecholaminergic polymorphic ventricular tachycardia 5.

What condition is associated with TRDN p.Ala95Val (c.284C>T)?

TRDN p.Ala95Val (c.284C>T) is associated with catecholaminergic polymorphic ventricular tachycardia 5 (ClinVar).

How common is TRDN p.Ala95Val (c.284C>T) in the general population?

TRDN p.Ala95Val (c.284C>T) is very rare (popmax 0.0036%, sas) (gnomAD).

What do computational predictors say about TRDN p.Ala95Val (c.284C>T)?

AlphaMissense predicts ambiguous (score 0.3532) — an in-silico prediction, not a clinical call.

TRDN p.Ala95Val

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.284C>T · rs764770921 · VCV811386

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3532 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0036%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

catecholaminergic polymorphic ventricular tachycardia 5

Computational evidence

Protein change
AlphaMissense	0.3532	ambiguous
REVEL	0.145	moderately benign-leaning
SaProt	LLR -3.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	21.5	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 0.0036% South Asian · 3/83,290 alleles

Filtering AF 0.000957% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000465%

Overall 0.000383% 6/1,565,562 alleles · very rare exomes 5/1,414,678 · genomes 1/150,884 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0036%	27,763
Admixed American	0.00186%	53,682
European (non-Finnish)	0.000173%	577,287

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.Ala95Val
Coding: c.284C>T
MANE Select: NM_006073
dbSNP: rs764770921
Type: single nucleotide variant
Location: chr6:123548561 (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 5 — 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 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 c.1051+1G>A Uncertain significance ★★ same condition
TRDN c.1136-1G>A 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-ala95val (accessed [today's date]).

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