GTF2E2 p.Asp187=
c.561C>T · rs760741546 · VCV2963585
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00187%, amr)
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 5.8 | GERP 3.9, phastCons 1 |
| Overall | ||
| CADD | 10.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00187%
Admixed American · 1/53,342 alleles
Filtering AF
8.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.3e-05%
Overall
0.000367%
5/1,362,834 alleles · very rare
exomes 5/1,211,568 · genomes 0/151,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00187% | 53,342 |
| African / African-American | 0.00146% | 68,688 |
| European (non-Finnish) | 0.000309% | 323,417 |
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
- GTF2E2
- Protein
- p.Asp187=
- Coding
- c.561C>T
- MANE Select
- NM_002095
- dbSNP
- rs760741546
- Type
- single nucleotide variant
- Location
- chr8:30607139 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI 0.40 (gnomAD)
- Structure
- AlphaFold pLDDT 68.97 · 46 PDB
- Residue 187
- a UniProt-annotated variant site (in ttd6; reduction in the levels of both tfiie-alpha and tfiie-beta subunits of the tfiie complex in patient cells; reduced phosphorylation of tfiie-alpha observed in patient cells); an α-helix
Similar variants
- GTF2E2 p.Asp187Tyr Pathogenic ★ same residue
- GTF2E2 p.Ala138Thr Uncertain significance ★★ ⚠ same type
- GTF2E2 p.Ala278Ser Uncertain significance ★★ ⚠ same type
- GTF2E2 p.Arg25Cys Uncertain significance ★★ ⚠ same type
- GTF2E2 p.Arg269Cys Uncertain significance ★★ ⚠ same type
- GTF2E2 p.Gly47Ala Uncertain significance ★★ ⚠ same type
- GTF2E2 p.His158Arg Uncertain significance ★★ ⚠ same type
- GTF2E2 p.Lys197Arg 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/gtf2e2-p-asp187 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown