TRRAP p.Pro2272=
c.6816C>G · rs143322478 · VCV1903133
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0574%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.073 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.25 | GERP -3.6, phastCons 0.98 |
| Overall | ||
| CADD | 5.972 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0574%
African / African-American · 43/74,942 alleles
Filtering AF
0.0437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.039%
Overall
0.00291%
47/1,614,130 alleles · ultra-rare
exomes 27/1,461,890 · genomes 20/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0574% | 1,743 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| Admixed American | 0.00167% | 60,012 |
| European (non-Finnish) | 8.47e-05% | 1,180,054 |
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.Pro2272=
- Coding
- c.6816C>G
- MANE Select
- NM_001375524
- dbSNP
- rs143322478
- Type
- single nucleotide variant
- Location
- chr7:98962414 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 2272
- an α-helix; the 'interaction with tp53' region
Similar variants
- 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
- TRRAP c.8247+5G>T 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-pro2272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown