TRPC3 p.Arg41Trp
c.121A>T · VCV4694315
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00143%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.361 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 41 kb · p 1.4e-05 · regional, not allelic |
| Overall | ||
| CADD | 24.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00143%
South Asian · 1/69,966 alleles
Filtering AF
0.000266%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000171%
Overall
0.000554%
8/1,444,624 alleles · very rare
exomes 8/1,292,862 · genomes 0/151,762 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00143% | 69,966 |
| European (non-Finnish) | 0.000639% | 156,456 |
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.Arg41Trp
- Coding
- c.121A>T
- MANE Select
- NM_001130698
- Type
- single nucleotide variant
- Location
- chr4:121951560 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 41
- the 'disordered' region
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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-arg41trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown