TRIOBP p.Pro663=
c.1989T>C · rs530563313 · VCV1193765
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0285%, sas)
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 -20 | GERP -2.8 |
| Overall | ||
| CADD | 1.888 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0285%
South Asian · 25/87,606 alleles
Filtering AF
0.0198%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0169%
Overall
0.00303%
47/1,549,438 alleles · ultra-rare
exomes 32/1,431,452 · genomes 15/117,986 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0285% | 3,504 |
| African / African-American | 0.0129% | 7,770 |
| Remaining individualsnot grpmax-eligible | 0.0067% | 14,922 |
| Finnishnot grpmax-eligible | 0.0067% | 14,934 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00362% | 27,606 |
| Admixed American | 0.00181% | 55,274 |
| European (non-Finnish) | 0.000348% | 287,205 |
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
- TRIOBP
- Protein
- p.Pro663=
- Coding
- c.1989T>C
- MANE Select
- NM_001039141
- dbSNP
- rs530563313
- Type
- single nucleotide variant
- Location
- chr22:37724545 (GRCh38)
- Gene constraint
- LOEUF 0.865 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 40.77
- Residue 663
- the 'disordered' region
Similar variants
- TRIOBP c.5184+1G>A Pathogenic/Likely pathogenic ★★ same type
- TRIOBP p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
- TRIOBP p.Arg1068Ter Pathogenic/Likely pathogenic ★★ same type
- TRIOBP p.Arg1117Ter Pathogenic ★★ same type
- TRIOBP p.Arg1745Ter Likely pathogenic ★★ same type
- TRIOBP p.Arg347Ter Pathogenic ★★ same type
- TRIOBP p.Arg399Ter Pathogenic/Likely pathogenic ★★ same type
- TRIOBP p.Arg448Ter Pathogenic ★★ 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/triobp-p-pro663 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown