TRPC3 p.Ser820Phe
c.2459C>T · rs377662018 · VCV1932179
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00221%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.343 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 1.3, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 22 kb · p 0.21 · regional, not allelic |
| Overall | ||
| CADD | 22.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00221%
European (non-Finnish) · 26/1,176,028 alleles
Filtering AF
0.00154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00131%
Overall
0.00168%
27/1,604,486 alleles · very rare
exomes 27/1,452,256 · genomes 0/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00221% | 45,232 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,118 |
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.Ser820Phe
- Coding
- c.2459C>T
- MANE Select
- NM_001130698
- dbSNP
- rs377662018
- Type
- single nucleotide variant
- Location
- chr4:121902856 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
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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-ser820phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown