TRIM28 p.Pro618=
c.1854G>A · rs139425078 · VCV2650601
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0461%, sas)
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 -3.4 | GERP -2.7 |
| Overall | ||
| CADD | 5.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0461%
South Asian · 42/91,088 alleles
Filtering AF
0.035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0311%
Overall
0.0273%
441/1,613,974 alleles · ultra-rare
exomes 418/1,461,722 · genomes 23/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0461% | 2,169 |
| European (non-Finnish) | 0.0319% | 3,130 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.005% | 20,006 |
| East Asian | 0.00446% | 22,433 |
| African / African-American | 0.004% | 25,005 |
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.Pro618=
- Coding
- c.1854G>A
- MANE Select
- NM_005762
- dbSNP
- rs139425078
- Type
- single nucleotide variant
- Location
- chr19:58549522 (GRCh38)
- Gene constraint
- LOEUF 0.17 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 67.59 · 10 PDB
- Residue 618
- a UniProt-annotated variant site (risk factor for wt7); the 'disordered' region
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-pro618 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown