TRPM6 p.Ser705=
c.2115G>C · VCV3621262
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
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 -0.57 | GERP -3.9 |
| Overall | ||
| CADD | 2.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,856 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000277%
Overall
0.000124%
2/1,613,942 alleles · very rare
exomes 2/1,461,874 · genomes 0/152,068 · 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
- TRPM6
- Protein
- p.Ser705=
- Coding
- c.2115G>C
- MANE Select
- NM_017662
- Type
- single nucleotide variant
- Location
- chr9:74800377 (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-ser705 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown