TRRAP p.Val2253=
c.6759C>T · rs56091446 · VCV713101
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.42%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.6 |
| Overall | ||
| CADD | 0.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.42%
East Asian · 1,985/44,866 alleles
Filtering AF
4.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.2%
Overall
0.134%
2,164/1,614,198 alleles · low-frequency
exomes 1,913/1,461,888 · genomes 251/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.42% | 23 |
| Remaining individualsnot grpmax-eligible | 0.173% | 579 |
| South Asian | 0.0296% | 3,374 |
| Admixed American | 0.0183% | 5,458 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| African / African-American | 0.00267% | 37,522 |
| European (non-Finnish) | 0.00254% | 39,334 |
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
- TRRAP
- Protein
- p.Val2253=
- Coding
- c.6759C>T
- MANE Select
- NM_001375524
- dbSNP
- rs56091446
- Type
- single nucleotide variant
- Location
- chr7:98962357 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 2253
- an α-helix; the 'interaction with tp53' region
Similar variants
- TRRAP p.Val2253Ile Uncertain significance ★ same residue
- TRRAP p.Arg1035Gln Pathogenic/Likely pathogenic ★★ same type
- TRRAP p.Glu1104Gly Pathogenic/Likely pathogenic ★★ same type
- TRRAP p.Glu1106Lys Likely pathogenic ★★ same type
- TRRAP p.Met3318Val Pathogenic/Likely pathogenic ★★ same type
- TRRAP p.Val1030Ile Likely pathogenic ★★ same type
- TRRAP c.2622+3A>G Uncertain significance ★★ same type
- TRRAP c.7176+4A>G 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/trrap-p-val2253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown