TRRAP p.Pro216Leu
c.647C>T · VCV3764482
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
AlphaMissense
likely pathogenic
0.9676 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9676 | likely pathogenic |
|---|---|---|
| REVEL | 0.5 | indeterminate |
| SaProt | — | not scored · why |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.61 | unconstrained · MANE · 29 kb · p 1.3e-20 · regional, not allelic |
| Overall | ||
| CADD | 29.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TRRAP
- Protein
- p.Pro216Leu
- Coding
- c.647C>T
- MANE Select
- NM_001375524
- Type
- single nucleotide variant
- Location
- chr7:98899435 (GRCh38)
- Gene constraint
- LOEUF 0.115 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Similar variants
- TRRAP p.Pro216= Likely benign ★ 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-pro216leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown