TRDN p.Pro352=
c.1056G>A · rs558713666 · VCV1778612
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00339%, amr)
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 -1.4 | GERP -4.3 |
| Overall | ||
| CADD | 2.717 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00339%
Admixed American · 2/58,950 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000834%
Overall
0.00156%
25/1,604,136 alleles · very rare
exomes 19/1,452,406 · genomes 6/151,730 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00339% | 29,475 |
| European (non-Finnish) | 0.00162% | 61,817 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,032 |
| Finnishnot grpmax-eligible | 0.00158% | 63,412 |
| African / African-American | 0.00134% | 74,560 |
| South Asian | 0.00111% | 89,742 |
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.Pro352=
- Coding
- c.1056G>A
- MANE Select
- NM_006073
- dbSNP
- rs558713666
- Type
- single nucleotide variant
- Location
- chr6:123393673 (GRCh38)
- Gene constraint
- LOEUF 1.359 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 47.65
- Residue 352
- the 'disordered' region
Similar variants
- TRDN p.Pro352Gln Uncertain significance ★★ ⚠ same residue
- TRDN p.Pro352Leu Uncertain significance ★★ ⚠ same residue
- TRDN p.Pro352Arg Uncertain significance ★ ⚠ same residue
- TRDN p.Pro352Ser Likely benign ★ 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
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-pro352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown