TRPC6 p.Ala276Ser
c.826G>T · VCV3694547
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2748 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2748 | likely benign |
|---|---|---|
| REVEL | 0.676 | pathogenic-leaning |
| SaProt | LLR -10.00 | damaging |
| ⇒ REVEL and SaProt call this damaging; AlphaMissense does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.82 | unconstrained · MANE · 28 kb · p 1.3e-05 · regional, not allelic |
| Overall | ||
| CADD | 26.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TRPC6
- Protein
- p.Ala276Ser
- Coding
- c.826G>T
- MANE Select
- NM_004621
- Type
- single nucleotide variant
- Location
- chr11:101504143 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
- Residue 276
- an α-helix
Similar variants
- TRPC6 p.Arg175Gln Likely pathogenic ★★ ⚠ same type
- TRPC6 p.Arg175Trp Pathogenic/Likely pathogenic ★★ same type
- TRPC6 p.Arg895Cys Pathogenic ★★ same type
- TRPC6 p.Arg895Leu Pathogenic ★★ same type
- TRPC6 p.Gln869Ter Pathogenic/Likely pathogenic ★★ same type
- TRPC6 p.Gln889Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
- TRPC6 p.Glu897Lys Pathogenic/Likely pathogenic ★★ same type
- TRPC6 p.Pro112Gln Pathogenic ★★ ⚠ same type
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-ala276ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown