TRPC3 p.His68=
c.204C>T · rs1355801342 · VCV2898541
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, afr)
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 -4.2 | GERP -2 |
| Overall | ||
| CADD | 9.727 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
African / African-American · 10/64,194 alleles
Filtering AF
0.00845%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00122%
16/1,314,568 alleles · ultra-rare
exomes 16/1,163,002 · genomes 0/151,566 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0156% | 6,419 |
| South Asian | 0.00429% | 23,333 |
| Remaining individualsnot grpmax-eligible | 0.0041% | 24,361 |
| European (non-Finnish) | 0.000193% | 516,817 |
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.His68=
- Coding
- c.204C>T
- MANE Select
- NM_001130698
- dbSNP
- rs1355801342
- Type
- single nucleotide variant
- Location
- chr4:121951477 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 68
- the 'disordered' region
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-his68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown