TRPC6 p.Thr296=
c.888G>A · rs144891994 · VCV259464
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.08%, amr)
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 -3.8 | GERP -4.1 |
| Overall | ||
| CADD | 6.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.08%
Admixed American · 48/60,002 alleles
Filtering AF
0.0619%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0555%
Overall
0.034%
549/1,613,998 alleles · ultra-rare
exomes 506/1,461,808 · genomes 43/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.08% | 1,250 |
| European (non-Finnish) | 0.039% | 2,565 |
| Middle Eastern | 0.033% | 3,030 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,677 |
| African / African-American | 0.0267% | 3,750 |
| South Asian | 0.0022% | 45,532 |
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.Thr296=
- Coding
- c.888G>A
- MANE Select
- NM_004621
- dbSNP
- rs144891994
- Type
- single nucleotide variant
- Location
- chr11:101504081 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
- Residue 296
- 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-thr296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown