TGM2 p.Pro686=
c.2058C>T · rs144501038 · VCV735348
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0853%, nfe)
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 -2.7 | GERP -4.3 |
| Overall | ||
| CADD | 2.068 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0853%
European (non-Finnish) · 1,006/1,179,894 alleles
Filtering AF
0.0808%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0791%
Overall
0.0666%
1,074/1,613,212 alleles · ultra-rare
exomes 1,033/1,461,004 · genomes 41/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0853% | 1,173 |
| Remaining individualsnot grpmax-eligible | 0.0753% | 1,328 |
| Admixed American | 0.0183% | 5,452 |
| African / African-American | 0.00534% | 18,732 |
| Finnishnot grpmax-eligible | 0.00469% | 21,328 |
| East Asian | 0.00223% | 44,880 |
| South Asian | 0.00221% | 45,345 |
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.Pro686=
- Coding
- c.2058C>T
- MANE Select
- NM_004613
- dbSNP
- rs144501038
- Type
- single nucleotide variant
- Location
- chr20:38130225 (GRCh38)
- Gene constraint
- LOEUF 0.902 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.91 · 14 PDB
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-pro686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown