TRPC6 p.Val646=
c.1938G>A · VCV3598797
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000848%, nfe)
Conditions
1
focal segmental glomerulosclerosis 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -0.9, phastCons 1 |
| Overall | ||
| CADD | 7.905 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000848%
European (non-Finnish) · 10/1,179,782 alleles
Filtering AF
0.000429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.00062%
10/1,613,512 alleles · very rare
exomes 5/1,461,464 · genomes 5/152,048 · 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
- TRPC6
- Protein
- p.Val646=
- Coding
- c.1938G>A
- MANE Select
- NM_004621
- Type
- single nucleotide variant
- Location
- chr11:101473580 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
- Residue 646
- an α-helix
Similar variants
- TRPC6 p.Arg175Gln Likely pathogenic ★★ ⚠ same condition
- TRPC6 p.Arg175Trp Pathogenic/Likely pathogenic ★★ same condition
- TRPC6 p.Arg895Cys Pathogenic ★★ same condition
- TRPC6 p.Arg895Leu Pathogenic ★★ same condition
- TRPC6 p.Gln889Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- TRPC6 p.Glu897Lys Pathogenic/Likely pathogenic ★★ same condition
- TRPC6 p.Pro112Gln Pathogenic ★★ ⚠ same condition
- TRPC6 c.170+5G>C Uncertain significance ★★ same condition
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/trpc6-p-val646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown