TRDN p.Ala435=
c.1305G>A · rs1170118704 · VCV737013
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0033%, sas)
Conditions
2
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 4.4 | GERP -0.25, phastCons 1 |
| Overall | ||
| CADD | 9.052 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0033%
South Asian · 3/90,976 alleles
Filtering AF
0.000876%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.00118%
19/1,612,432 alleles · very rare
exomes 16/1,460,406 · genomes 3/152,026 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0033% | 30,325 |
| Finnishnot grpmax-eligible | 0.00313% | 31,938 |
| East Asian | 0.00223% | 44,766 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,414 |
| European (non-Finnish) | 0.00102% | 98,258 |
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.Ala435=
- Coding
- c.1305G>A
- MANE Select
- NM_006073
- dbSNP
- rs1170118704
- Type
- single nucleotide variant
- Location
- chr6:123366151 (GRCh38)
- Gene constraint
- LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 47.65
- Residue 435
- the 'disordered' region
Similar variants
- TRDN p.Ala435Glu Uncertain significance ★★ ⚠ same residue
- TRDN p.Ala435Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown