TRPS1 p.Pro817=
c.2451G>A · rs770052582 · VCV2930362
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00666%, afr)
Conditions
1
trichorhinophalangeal syndrome type I
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 -5.9 | GERP -5.6 |
| Overall | ||
| CADD | 1.426 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00666%
African / African-American · 5/75,068 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00118%
19/1,614,216 alleles · very rare
exomes 11/1,461,882 · genomes 8/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00666% | 15,014 |
| Admixed American | 0.005% | 20,013 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| South Asian | 0.00439% | 22,770 |
| East Asian | 0.00223% | 44,870 |
| European (non-Finnish) | 0.000254% | 393,345 |
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
- TRPS1
- Protein
- p.Pro817=
- Coding
- c.2451G>A
- MANE Select
- NM_014112
- dbSNP
- rs770052582
- Type
- single nucleotide variant
- Location
- chr8:115587250 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.12
- Residue 817
- the 'mediates interaction with gli3' region
Similar variants
- TRPS1 c.2097-2A>C Pathogenic/Likely pathogenic ★★ same condition
- TRPS1 p.Ala932Thr Pathogenic/Likely pathogenic ★★ same condition
- TRPS1 p.Ala932Val Pathogenic ★★ same condition
- TRPS1 p.Arg257Ter Pathogenic ★★ same condition
- TRPS1 p.Arg544Ter Pathogenic ★★ same condition
- TRPS1 p.Arg624Ter Pathogenic ★★ same condition
- TRPS1 p.Arg696Ter Pathogenic ★★ same condition
- TRPS1 p.Arg921Gln Pathogenic ★★ same condition
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/trps1-p-pro817 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown