Is TRDN p.Ile433= (c.1299T>C) pathogenic?

TRDN p.Ile433= (c.1299T>C) is classified Likely benign in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2016-11-25). Very rare (popmax 0.000254%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Ile433= (c.1299T>C)?

TRDN p.Ile433= (c.1299T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is TRDN p.Ile433= (c.1299T>C) in the general population?

TRDN p.Ile433= (c.1299T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

TRDN p.Ile433=

c.1299T>C · rs1443094358 · VCV519362

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 3.2	GERP -1.6, phastCons 0.021
Overall
CADD	3.886	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,270 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,014 alleles · very rare exomes 3/1,460,718 · genomes 0/152,296 · joint denominator

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.Ile433=
Coding: c.1299T>C
MANE Select: NM_006073
dbSNP: rs1443094358
Type: single nucleotide variant
Location: chr6:123366157 (GRCh38)
Gene constraint: LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 47.65
Residue 433: 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

Similar variants

TRDN p.Ile433Thr Uncertain significance ★ ⚠ same residue
TRDN p.Glu168Ter Pathogenic/Likely pathogenic ★★ same condition
TRDN p.Lys177Ter Pathogenic ★★ same condition
TRDN c.1166-2A>C Uncertain significance ★★ same condition
TRDN c.1273+4T>C Uncertain significance ★★ same condition
TRDN c.1273+5G>A Uncertain significance ★★ same condition
TRDN c.1322-10T>A Uncertain significance ★★ same condition
TRDN c.1537+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-ile433 (accessed [today's date]).

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