TRPM2 p.Lys116=
c.348G>A · rs45479791 · VCV785673
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.73%, 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 0.79 | GERP -3.1, phastCons 1 |
| Overall | ||
| CADD | 5.279 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.73%
African / African-American · 2,050/75,062 alleles
Filtering AF
2.63%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.59%
Overall
0.139%
2,243/1,614,246 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.73% | 37 |
| Remaining individualsnot grpmax-eligible | 0.142% | 702 |
| Admixed American | 0.132% | 760 |
| Middle Eastern | 0.099% | 1,010 |
| South Asian | 0.00659% | 15,182 |
| East Asian | 0.00223% | 44,888 |
| European (non-Finnish) | 0.00102% | 98,337 |
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
- TRPM2
- Protein
- p.Lys116=
- Coding
- c.348G>A
- MANE Select
- NM_003307
- dbSNP
- rs45479791
- Type
- single nucleotide variant
- Location
- chr21:44364207 (GRCh38)
- Gene constraint
- LOEUF 1.047 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.51 · 15 PDB
- Residue 116
- a turn
Similar variants
- TRPM2 c.1932+141G>A Benign ★★ same type
- TRPM2 c.1933-10T>C Benign ★★ same type
- TRPM2 c.2322-35T>C Benign ★★ same type
- TRPM2 c.2538+14C>T Benign ★★ same type
- TRPM2 c.2962+96A>G Benign ★★ same type
- TRPM2 c.3146+68T>C Benign ★★ same type
- TRPM2 c.3147-20T>C Benign ★★ same type
- TRPM2 c.3549+8C>T Likely benign ★★ 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/trpm2-p-lys116 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown