TRPM8 p.Pro916=
c.2748C>A · rs145230970 · VCV785996
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.89%, 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 0.77 | GERP 0.21, phastCons 1 |
| Overall | ||
| CADD | 8.518 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.89%
African / African-American · 2,918/75,034 alleles
Filtering AF
3.77%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.72%
Overall
0.216%
3,492/1,614,094 alleles · low-frequency
exomes 1,783/1,461,852 · genomes 1,709/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.89% | 26 |
| Admixed American | 0.39% | 256 |
| Remaining individualsnot grpmax-eligible | 0.312% | 321 |
| Middle Eastern | 0.148% | 674 |
| European (non-Finnish) | 0.0108% | 9,291 |
| South Asian | 0.00989% | 10,116 |
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
- TRPM8
- Protein
- p.Pro916=
- Coding
- c.2748C>A
- MANE Select
- NM_024080
- dbSNP
- rs145230970
- Type
- single nucleotide variant
- Location
- chr2:233983211 (GRCh38)
- Gene constraint
- LOEUF 0.945 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.42 · 6 PDB
Similar variants
- TRPM8 p.Arg247Thr Benign ★★ same type
- TRPM8 p.Asn821Ser Benign ★★ same type
- TRPM8 p.Glu545= Benign ★★ same type
- TRPM8 p.Leu226= Benign ★★ same type
- TRPM8 p.Met462Thr Benign ★★ ⚠ same type
- TRPM8 p.Ala1071Pro Uncertain significance ★ ⚠ same type
- TRPM8 p.Ala1071Val Uncertain significance ★ ⚠ same type
- TRPM8 p.Ala172Thr Uncertain significance ★ ⚠ 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/trpm8-p-pro916 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown