TRPC3 p.Ile438Phe
c.1312A>T · rs150143801 · VCV2038530
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.181%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.179 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -1.8, phastCons 1 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 41 kb · p 1.4e-05 · regional, not allelic |
| Overall | ||
| CADD | 18.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.181%
European (non-Finnish) · 2,137/1,178,820 alleles
Filtering AF
0.175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.172%
Overall
0.14%
2,261/1,612,480 alleles · rare
exomes 2,136/1,460,274 · genomes 125/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.181% | 552 |
| Remaining individualsnot grpmax-eligible | 0.0865% | 1,156 |
| African / African-American | 0.0413% | 2,419 |
| Admixed American | 0.0333% | 2,999 |
| Finnishnot grpmax-eligible | 0.0266% | 3,764 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.0011% | 90,878 |
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.Ile438Phe
- Coding
- c.1312A>T
- MANE Select
- NM_001130698
- dbSNP
- rs150143801
- Type
- single nucleotide variant
- Location
- chr4:121914809 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 438
- 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-ile438phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown