TRPC6 p.His145=
c.435T>C · rs200589012 · VCV2957869
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0549%, sas)
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 0.15 | GERP -4.1, phastCons 0.33 |
| Overall | ||
| CADD | 4.499 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0549%
South Asian · 50/91,082 alleles
Filtering AF
0.0427%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0385%
Overall
0.00465%
75/1,614,002 alleles · ultra-rare
exomes 71/1,461,812 · genomes 4/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0549% | 1,822 |
| Middle Eastern | 0.0164% | 6,084 |
| European (non-Finnish) | 0.00178% | 56,191 |
| Admixed American | 0.00167% | 59,978 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| Finnishnot grpmax-eligible | 0.00156% | 64,040 |
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.His145=
- Coding
- c.435T>C
- MANE Select
- NM_004621
- dbSNP
- rs200589012
- Type
- single nucleotide variant
- Location
- chr11:101504534 (GRCh38)
- Gene constraint
- LOEUF 0.708 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.98 · 6 PDB
Similar variants
- TRPC6 p.His145Arg Uncertain significance ★ ⚠ same residue
- 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
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-his145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown