TRPC3 p.Thr705Ser
c.2113A>T · rs769488090 · VCV2043556
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0414%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.427 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.56 | unconstrained · MANE · 6,020 bp · p 7.1e-13 · regional, not allelic |
| Overall | ||
| CADD | 19.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0414%
Admixed American · 23/55,554 alleles
Filtering AF
0.0283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0239%
Overall
0.00144%
23/1,598,056 alleles · ultra-rare
exomes 20/1,445,900 · genomes 3/152,156 · joint denominator
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.Thr705Ser
- Coding
- c.2113A>T
- MANE Select
- NM_001130698
- dbSNP
- rs769488090
- Type
- single nucleotide variant
- Location
- chr4:121904462 (GRCh38)
- Gene constraint
- LOEUF 0.751 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.42 · 19 PDB
- Residue 705
- 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-thr705ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown