TRPC3 p.Gln593Arg
c.1778A>G · rs200366233 · VCV1704512
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.099 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP -1.7, phastCons 1 |
| Regional constraint | o/e 0.56 | unconstrained · MANE · 6,020 bp · p 7.1e-13 · regional, not allelic |
| Overall | ||
| CADD | 18.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,054 alleles
Filtering AF
0.00232%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00248%
40/1,613,282 alleles · ultra-rare
exomes 38/1,461,048 · genomes 2/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,054 |
| European (non-Finnish) | 0.00314% | 31,876 |
| South Asian | 0.0022% | 45,532 |
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.Gln593Arg
- Coding
- c.1778A>G
- MANE Select
- NM_001130698
- dbSNP
- rs200366233
- Type
- single nucleotide variant
- Location
- chr4:121910168 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 593
- 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-gln593arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown