Is TRDN p.Ala202Val (c.605C>T) pathogenic?

TRDN p.Ala202Val (c.605C>T) is classified Conflicting classifications of pathogenicity in TRDN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-09). AlphaMissense: likely benign (0.1085); Very rare (popmax 0.00954%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Ala202Val (c.605C>T)?

TRDN p.Ala202Val (c.605C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Ala202Val (c.605C>T) in the general population?

TRDN p.Ala202Val (c.605C>T) is very rare (popmax 0.00954%, amr) (gnomAD).

What do computational predictors say about TRDN p.Ala202Val (c.605C>T)?

AlphaMissense predicts likely benign (score 0.1085) — an in-silico prediction, not a clinical call.

TRDN p.Ala202Val

c.605C>T · rs765653366 · VCV1493665

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00954%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1085	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.47, phastCons 0.68
Regional constraint	o/e 1.09	unconstrained · MANE · 418 kb · p 0.011 · regional, not allelic
Overall
CADD	17.61	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 0.00954% Admixed American · 5/52,384 alleles

Filtering AF 0.00374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00196% 29/1,478,934 alleles · very rare exomes 26/1,326,996 · genomes 3/151,938 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00954%	10,477
Ashkenazi Jewishnot grpmax-eligible	0.00724%	13,806
Finnishnot grpmax-eligible	0.00329%	30,382
African / African-American	0.00278%	35,991
East Asian	0.00233%	42,964
Remaining individualsnot grpmax-eligible	0.00175%	57,164
European (non-Finnish)	0.00148%	67,466

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.Ala202Val
Coding: c.605C>T
MANE Select: NM_006073
dbSNP: rs765653366
Type: single nucleotide variant
Location: chr6:123512308 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 202: the 'disordered' region

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.Ala202= Likely benign ★★ same residue
TRDN p.Ala202Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala202val (accessed [today's date]).

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