TRPM6 p.Ala172=
c.516G>A · rs370745121 · VCV2697178
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00933%, afr)
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 -20 | GERP -3.7 |
| Overall | ||
| CADD | 0.384 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00933%
African / African-American · 7/75,016 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.00266%
43/1,614,038 alleles · very rare
exomes 40/1,461,808 · genomes 3/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00933% | 10,717 |
| Admixed American | 0.00833% | 12,004 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| East Asian | 0.00223% | 44,868 |
| European (non-Finnish) | 0.00212% | 47,198 |
| South Asian | 0.0011% | 91,080 |
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
- TRPM6
- Protein
- p.Ala172=
- Coding
- c.516G>A
- MANE Select
- NM_017662
- dbSNP
- rs370745121
- Type
- single nucleotide variant
- Location
- chr9:74840052 (GRCh38)
- Gene constraint
- LOEUF 0.494 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 65.03
Similar variants
- TRPM6 c.1308+7T>G Pathogenic ★★ same type
- TRPM6 c.841+1G>A Pathogenic ★★ same type
- TRPM6 p.Arg1772Ter Pathogenic ★★ same type
- TRPM6 p.Arg340Ter Pathogenic/Likely pathogenic ★★ same type
- TRPM6 p.Arg56Ter Pathogenic/Likely pathogenic ★★ same type
- TRPM6 p.Cys1429Ter Pathogenic/Likely pathogenic ★★ same type
- TRPM6 p.Gln1212Ter Likely pathogenic ★★ same type
- TRPM6 p.Tyr574Ter 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/trpm6-p-ala172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown