TRPC3 p.Ile442=
c.1326C>T · rs188254399 · VCV2023679
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP -4.4 |
| Overall | ||
| CADD | 0.812 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,812 alleles
Filtering AF
0.00727%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.000931%
15/1,610,576 alleles · ultra-rare
exomes 15/1,458,308 · genomes 0/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,402 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,150 |
| African / African-American | 0.00133% | 75,000 |
| European (non-Finnish) | 0.000425% | 235,480 |
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.Ile442=
- Coding
- c.1326C>T
- MANE Select
- NM_001130698
- dbSNP
- rs188254399
- Type
- single nucleotide variant
- Location
- chr4:121914795 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 442
- an α-helix
Similar variants
- TRPC3 p.Arg381Cys Uncertain significance ★★ same type
- TRPC3 p.Arg795Gln Uncertain significance ★★ same type
- TRPC3 p.Asn728Ser Uncertain significance ★★ same type
- TRPC3 p.Glu901Lys Uncertain significance ★★ same type
- TRPC3 p.Ile629Val Uncertain significance ★★ same type
- TRPC3 p.Leu905Val Uncertain significance ★★ same type
- TRPC3 p.Lys710Arg Uncertain significance ★★ same type
- TRPC3 p.Pro444Ser 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/trpc3-p-ile442 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown