TPRN p.Val643=
c.1929G>A · rs115446132 · VCV165577
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.43%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.76 | GERP 1.5, phastCons 0.036 |
| Overall | ||
| CADD | 4.188 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.43%
African / African-American · 1,073/74,828 alleles
Filtering AF
1.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.33%
Overall
0.077%
1,236/1,605,826 alleles · low-frequency
exomes 589/1,453,500 · genomes 647/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.43% | 70 |
| Admixed American | 0.18% | 556 |
| Remaining individualsnot grpmax-eligible | 0.0788% | 1,269 |
| Middle Eastern | 0.0332% | 3,012 |
| East Asian | 0.00225% | 44,400 |
| European (non-Finnish) | 0.000425% | 235,310 |
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.Val643=
- Coding
- c.1929G>A
- MANE Select
- NM_001128228
- dbSNP
- rs115446132
- Type
- single nucleotide variant
- Location
- chr9:137192488 (GRCh38)
- Gene constraint
- LOEUF 1.099 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.27 · 1 PDB
- Residue 643
- 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-val643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown