TRPC5 p.Leu447=
c.1339C>T · rs371783296 · VCV2661217
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, nfe)
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 2.4 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 6.164 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
European (non-Finnish) · 208/893,913 alleles
Filtering AF
0.0206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.0181%
219/1,208,324 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0233% | 4,298 |
| Remaining individualsnot grpmax-eligible | 0.0147% | 6,791 |
| African / African-American | 0.0035% | 28,601 |
| Admixed American | 0.00219% | 45,704 |
| South Asian | 0.00177% | 56,577 |
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
- TRPC5
- Protein
- p.Leu447=
- Coding
- c.1339C>T
- MANE Select
- NM_012471
- dbSNP
- rs371783296
- Type
- single nucleotide variant
- Location
- chrX:111852336 (GRCh38)
- Structure
- AlphaFold pLDDT 73.82 · 30 PDB
- Residue 447
- an α-helix
Similar variants
- TRPC5 p.Ala929Thr Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg120Gln Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg175Cys Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg17Cys Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg17His Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg17Leu Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg222Cys Uncertain significance ★ ⚠ same type
- TRPC5 p.Arg263Lys Uncertain significance ★ ⚠ same type
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/trpc5-p-leu447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown