TPRN p.Pro230=
c.690C>G · rs1473487453 · VCV682347
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00143%, afr)
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 5.4 | GERP -0.32, phastCons 1 |
| Overall | ||
| CADD | 6.971 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00143%
African / African-American · 1/69,714 alleles
Filtering AF
0.000535%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000391%
Overall
0.000832%
12/1,441,792 alleles · very rare
exomes 8/1,289,716 · genomes 4/152,076 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00143% | 69,714 |
| European (non-Finnish) | 0.000996% | 100,371 |
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
- TPRN
- Protein
- p.Pro230=
- Coding
- c.690C>G
- MANE Select
- NM_001128228
- dbSNP
- rs1473487453
- Type
- single nucleotide variant
- Location
- chr9:137200022 (GRCh38)
- Gene constraint
- LOEUF 1.099 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.27 · 1 PDB
- Residue 230
- the 'disordered' region
Similar variants
- TPRN p.Gln414Ter Pathogenic ★★ same type
- TPRN c.1725+5G>A Uncertain significance ★★ same type
- TPRN p.Ala191Val Uncertain significance ★★ ⚠ same type
- TPRN p.Ala302Asp Uncertain significance ★★ ⚠ same type
- TPRN p.Ala390Ser Uncertain significance ★★ ⚠ same type
- TPRN p.Ala695Thr Uncertain significance ★★ ⚠ same type
- TPRN p.Arg231Trp Uncertain significance ★★ ⚠ same type
- TPRN p.Arg284His 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/tprn-p-pro230 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown