TRPC6 p.Ala448=
c.1344C>A · rs554849365 · VCV301907
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 1.8 | GERP -0.54, phastCons 1 |
| Overall | ||
| CADD | 7.551 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,082 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000186%
3/1,614,018 alleles · very rare
exomes 1/1,461,782 · genomes 2/152,236 · 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.Ala448=
- Coding
- c.1344C>A
- MANE Select
- NM_004621
- dbSNP
- rs554849365
- Type
- single nucleotide variant
- Location
- chr11:101483115 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
- Residue 448
- 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-ala448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown