Is TRDN p.Pro28= (c.84C>T) pathogenic?

TRDN p.Pro28= (c.84C>T) is classified Likely benign in TRDN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-04). Rare (popmax 0.228%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Pro28= (c.84C>T)?

TRDN p.Pro28= (c.84C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is TRDN p.Pro28= (c.84C>T) in the general population?

TRDN p.Pro28= (c.84C>T) is rare (popmax 0.228%, afr) (gnomAD).

TRDN p.Pro28=

c.84C>T · rs145992727 · VCV228027

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.228%, afr)

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 1.4	GERP -2.3, phastCons 1
Overall
CADD	12.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.228% African / African-American · 171/75,034 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.189%

Overall 0.0136% 219/1,613,952 alleles · rare exomes 121/1,461,662 · genomes 98/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.228%	439
Remaining individualsnot grpmax-eligible	0.0368%	2,717
Admixed American	0.0283%	3,530
Finnishnot grpmax-eligible	0.00469%	21,337
European (non-Finnish)	0.000424%	235,973

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.Pro28=
Coding: c.84C>T
MANE Select: NM_006073
dbSNP: rs145992727
Type: single nucleotide variant
Location: chr6:123571071 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 28: 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 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
TRDN p.Met1Thr 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-pro28 (accessed [today's date]).

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