TRPC6 p.Ser606=
c.1818T>C · rs139187399 · VCV259457
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.723%, afr)
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 6.2 | GERP 0.84, phastCons 1 |
| Overall | ||
| CADD | 9.774 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.723%
African / African-American · 542/75,012 alleles
Filtering AF
0.672%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.652%
Overall
0.0371%
598/1,613,768 alleles · rare
exomes 289/1,461,484 · genomes 309/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.723% | 138 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,562 |
| Admixed American | 0.02% | 4,999 |
| South Asian | 0.0022% | 45,535 |
| European (non-Finnish) | 0.00017% | 589,894 |
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.Ser606=
- Coding
- c.1818T>C
- MANE Select
- NM_004621
- dbSNP
- rs139187399
- Type
- single nucleotide variant
- Location
- chr11:101473700 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
- Residue 606
- 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-ser606 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown