TRPC3 p.Ala559Pro
c.1675G>C · VCV4191599
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.915 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.37 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.56 | unconstrained · MANE · 6,020 bp · p 7.1e-13 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,804 alleles
Overall
6.2e-05%
1/1,613,834 alleles · very rare
exomes 1/1,461,556 · genomes 0/152,278 · 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
- TRPC3
- Protein
- p.Ala559Pro
- Coding
- c.1675G>C
- MANE Select
- NM_001130698
- Type
- single nucleotide variant
- Location
- chr4:121910271 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 559
- an α-helix
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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/trpc3-p-ala559pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown