PRX p.Pro733=
c.2199T>C · rs1277285038 · VCV1624635
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0197%, afr)
Conditions
1
Charcot-Marie-Tooth disease type 4
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 -12 | GERP -4.5 |
| Overall | ||
| CADD | 0.227 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0197%
African / African-American · 14/71,224 alleles
Filtering AF
0.0119%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00948%
Overall
0.00213%
34/1,595,226 alleles · ultra-rare
exomes 3/1,453,446 · genomes 31/141,780 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0197% | 5,087 |
| Middle Eastern | 0.0168% | 5,946 |
| East Asian | 0.00683% | 14,649 |
| Admixed American | 0.00512% | 19,535 |
| Finnishnot grpmax-eligible | 0.00318% | 31,482 |
| South Asian | 0.00111% | 89,988 |
| European (non-Finnish) | 0.000854% | 117,093 |
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
- PRX
- Protein
- p.Pro733=
- Coding
- c.2199T>C
- MANE Select
- NM_181882
- dbSNP
- rs1277285038
- Type
- single nucleotide variant
- Location
- chr19:40396153 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 733
- the '55 x 5 aa approximate tandem repeats of [lvmag]-[psreqc]-[edkl]-[livmap]-[aqkhrpe]; that may have a tripeptide spacer of [lv]-p-[ker]' region
Similar variants
- PRX c.184+2T>C Likely pathogenic ★★ same condition
- PRX p.Arg1070Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg196Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg364Ter Pathogenic ★★ same condition
- PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg464Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Arg897Ter Pathogenic/Likely 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/prx-p-pro733 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown