Is TRDN p.Ala268= (c.804A>G) pathogenic?

TRDN p.Ala268= (c.804A>G) is classified Likely benign in TRDN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-08). Ultra-rare (popmax 0.0221%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Ala268= (c.804A>G)?

TRDN p.Ala268= (c.804A>G) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Ala268= (c.804A>G) in the general population?

TRDN p.Ala268= (c.804A>G) is ultra-rare (popmax 0.0221%, sas) (gnomAD).

TRDN p.Ala268=

c.804A>G · rs748948862 · VCV1081154

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0221%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.74	GERP -1.3, phastCons 0.026
Overall
CADD	10.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0221% South Asian · 18/81,618 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.00136% 21/1,548,428 alleles · ultra-rare exomes 18/1,396,190 · genomes 3/152,238 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0221%	4,534
African / African-American	0.00278%	35,986
European (non-Finnish)	8.7e-05%	1,148,996

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.Ala268=
Coding: c.804A>G
MANE Select: NM_006073
dbSNP: rs748948862
Type: single nucleotide variant
Location: chr6:123497242 (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.Ala268Thr Uncertain significance ★ ⚠ same residue
TRDN p.Ala268Val 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-ala268 (accessed [today's date]).

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