TGM2 p.Pro217=
c.651C>G · rs45461691 · VCV786677
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.81%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.4 | GERP -4.8 |
| Overall | ||
| CADD | 0.226 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.81%
African / African-American · 2,860/75,012 alleles
Filtering AF
3.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.65%
Overall
0.217%
3,498/1,613,194 alleles · low-frequency
exomes 1,830/1,460,860 · genomes 1,668/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.81% | 26 |
| Middle Eastern | 0.34% | 294 |
| Admixed American | 0.31% | 322 |
| Remaining individualsnot grpmax-eligible | 0.293% | 341 |
| European (non-Finnish) | 0.0207% | 4,836 |
| East Asian | 0.00669% | 14,955 |
| South Asian | 0.0033% | 30,318 |
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
- TGM2
- Protein
- p.Pro217=
- Coding
- c.651C>G
- MANE Select
- NM_004613
- dbSNP
- rs45461691
- Type
- single nucleotide variant
- Location
- chr20:38147991 (GRCh38)
- Gene constraint
- LOEUF 0.902 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.91 · 14 PDB
- Residue 217
- an α-helix
Similar variants
- TGM2 c.433+3G>A Likely benign ★★ same type
- TGM2 p.Ala282= Benign ★★ same type
- TGM2 p.Ala390= Benign ★★ same type
- TGM2 p.Arg28= Benign ★★ same type
- TGM2 p.Arg377His Benign ★★ ⚠ same type
- TGM2 p.Arg76His Benign ★★ same type
- TGM2 p.Asp326= Benign ★★ same type
- TGM2 p.Ile416= 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/tgm2-p-pro217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown