TGFB2 p.His2=
c.6C>T · VCV4940389
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00224%, eas)
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 3.9 | GERP 0.94, phastCons 1 |
| Overall | ||
| CADD | 12.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00224%
East Asian · 1/44,700 alleles
Filtering AF
0.000125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.1e-05%
Overall
0.000504%
8/1,587,802 alleles · very rare
exomes 5/1,435,684 · genomes 3/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00224% | 44,700 |
| Admixed American | 0.00198% | 50,470 |
| African / African-American | 0.00137% | 73,092 |
| European (non-Finnish) | 0.000426% | 234,650 |
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
- TGFB2
- Protein
- p.His2=
- Coding
- c.6C>T
- MANE Select
- NM_003238
- Type
- single nucleotide variant
- Location
- chr1:218346707 (GRCh38)
- Gene constraint
- LOEUF 0.463 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 11 PDB
Similar variants
- TGFB2 p.His2Arg Uncertain significance ★ ⚠ same residue
- TGFB2 c.1086+2T>C Likely pathogenic ★★ same type
- TGFB2 c.346+1G>A Pathogenic/Likely pathogenic ★★ same type
- TGFB2 c.346+1G>T Likely pathogenic ★★ same type
- TGFB2 c.510+1G>A Likely pathogenic ★★ same type
- TGFB2 c.932+1G>A Pathogenic/Likely pathogenic ★★ same type
- TGFB2 c.933-1G>A Pathogenic/Likely pathogenic ★★ same type
- TGFB2 p.Arg131Ter Pathogenic/Likely 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/tgfb2-p-his2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown