TRDN p.Thr42=
c.126G>A · rs774324909 · VCV518556
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
Conditions
2
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 -8.7 | GERP -4 |
| Overall | ||
| CADD | 2.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/59,998 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00483%
Overall
0.00124%
20/1,613,858 alleles · ultra-rare
exomes 17/1,461,676 · genomes 3/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,500 |
| African / African-American | 0.00133% | 74,914 |
| European (non-Finnish) | 0.000932% | 107,262 |
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.Thr42=
- Coding
- c.126G>A
- MANE Select
- NM_006073
- dbSNP
- rs774324909
- Type
- single nucleotide variant
- Location
- chr6:123571029 (GRCh38)
- Gene constraint
- LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 47.65
Similar variants
- TRDN p.Thr42Met 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
- TRDN p.Lys177Ter 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-thr42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown