TRPC6 p.Ala404=
c.1212G>A · rs144085223 · VCV1554279
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0693%, 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 -14 | GERP -4.1 |
| Overall | ||
| CADD | 1.334 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0693%
African / African-American · 52/75,028 alleles
Filtering AF
0.0542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0489%
Overall
0.00551%
89/1,614,112 alleles · ultra-rare
exomes 54/1,461,828 · genomes 35/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0693% | 1,443 |
| South Asian | 0.034% | 2,938 |
| East Asian | 0.00223% | 44,874 |
| Admixed American | 0.00167% | 60,020 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.000254% | 393,335 |
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.Ala404=
- Coding
- c.1212G>A
- MANE Select
- NM_004621
- dbSNP
- rs144085223
- Type
- single nucleotide variant
- Location
- chr11:101489018 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
- Residue 404
- a UniProt-annotated variant site (increases calcium ion transport)
Similar variants
- TRPC6 p.Ala404Val Benign ★★ same residue
- 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
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-ala404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown