TRIM28 p.Pro716=
c.2148C>T · rs3816328 · VCV2789323
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 16.8%, amr) — too common for a highly-penetrant pathogenic allele
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 -4.5 | GERP -3 |
| Overall | ||
| CADD | 7.826 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
16.8%
Admixed American · 10,099/60,014 alleles
Filtering AF
16.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 16.4%
Overall
5.19%
83,801/1,614,016 alleles · common
exomes 73,042/1,461,870 · genomes 10,759/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 16.8% | 6 |
| African / African-American | 11.1% | 9 |
| South Asian | 11% | 9 |
| East Asian | 10.3% | 10 |
| Remaining individualsnot grpmax-eligible | 5.68% | 18 |
| Middle Eastern | 5.56% | 18 |
| Finnishnot grpmax-eligible | 4.43% | 23 |
| Ashkenazi Jewishnot grpmax-eligible | 4.26% | 23 |
| European (non-Finnish) | 3.62% | 28 |
| Amishnot grpmax-eligible | 2.3% | 43 |
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
- TRIM28
- Protein
- p.Pro716=
- Coding
- c.2148C>T
- MANE Select
- NM_005762
- dbSNP
- rs3816328
- Type
- single nucleotide variant
- Location
- chr19:58549990 (GRCh38)
- Gene constraint
- LOEUF 0.17 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.59 · 10 PDB
- Residue 716
- a UniProt-annotated variant site (risk factor for wt7); the bromo domain
Similar variants
- TRIM28 p.Ala537Val Uncertain significance ★★ ⚠ same type
- TRIM28 p.Arg412His Uncertain significance ★★ ⚠ same type
- TRIM28 p.Arg706Cys Uncertain significance ★★ ⚠ same type
- TRIM28 p.Arg767His Uncertain significance ★★ ⚠ same type
- TRIM28 p.Arg795Cys Uncertain significance ★★ ⚠ same type
- TRIM28 p.Asp231Tyr Uncertain significance ★★ ⚠ same type
- TRIM28 p.Glu798Asp Uncertain significance ★★ ⚠ same type
- TRIM28 p.Gly735Ala 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/trim28-p-pro716 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown