Is TRDN p.Tyr73= (c.219C>T) pathogenic?

TRDN p.Tyr73= (c.219C>T) is classified Likely benign in TRDN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-24). Very rare (popmax 0.000424%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TRDN p.Tyr73= (c.219C>T)?

TRDN p.Tyr73= (c.219C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TRDN p.Tyr73= (c.219C>T) in the general population?

TRDN p.Tyr73= (c.219C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

TRDN p.Tyr73=

c.219C>T · rs2534608934 · VCV1787547

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.2, phastCons 1
Overall
CADD	6.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,574 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,352 alleles · very rare exomes 5/1,461,126 · genomes 0/152,226 · 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.Tyr73=
Coding: c.219C>T
MANE Select: NM_006073
dbSNP: rs2534608934
Type: single nucleotide variant
Location: chr6:123570936 (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

Similar variants

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
TRDN c.1597+3A>G 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-tyr73 (accessed [today's date]).

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