TRPS1 p.Arg996=
c.2988G>A · rs202158991 · VCV593383
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0354%, amr)
Conditions
2
Trichorhinophalangeal syndrome, type III
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.131 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 9.251 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0354%
Admixed American · 21/59,282 alleles
Filtering AF
0.0237%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0199%
Overall
0.0018%
29/1,607,198 alleles · ultra-rare
exomes 13/1,455,116 · genomes 16/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0354% | 2,823 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,773 |
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.Arg996=
- Coding
- c.2988G>A
- MANE Select
- NM_014112
- dbSNP
- rs202158991
- Type
- single nucleotide variant
- Location
- chr8:115414920 (GRCh38)
- Gene constraint
- LOEUF 0.114 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.12
- Residue 996
- the 'disordered' region; the 'mediates interaction with rnf4' 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-arg996 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown