TRPC3 p.Pro58=
c.174G>T · rs548386120 · VCV2047162
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0491%, nfe)
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 -0.23 | GERP -0.17, phastCons 0.034 |
| Overall | ||
| CADD | 11.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0491%
European (non-Finnish) · 520/1,060,052 alleles
Filtering AF
0.0456%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0442%
Overall
0.04%
546/1,365,478 alleles · ultra-rare
exomes 488/1,213,774 · genomes 58/151,704 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0491% | 2,039 |
| Remaining individualsnot grpmax-eligible | 0.0234% | 4,277 |
| Admixed American | 0.0225% | 4,446 |
| African / African-American | 0.0107% | 9,306 |
| Finnishnot grpmax-eligible | 0.002% | 49,972 |
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.Pro58=
- Coding
- c.174G>T
- MANE Select
- NM_001130698
- dbSNP
- rs548386120
- Type
- single nucleotide variant
- Location
- chr4:121951507 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 58
- 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-pro58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown