PRX p.Pro588fs
c.1761del · VCV3780494
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 0.17, phastCons 0.42 |
| Region caveats | ||
| Repeat context | tandem | AGGGAGTTTCATCTCTGGGACTTTTGGAAGCTGCACTTCCGGGAGGTGCACATCGGGCACAGCCATCTCGGGCACCTTCGGGAGTTGCACCTCAGGGAGTTTCATCTC simple repeat · ambiguous alignment · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PRX
- Protein
- p.Pro588fs
- Coding
- c.1761del
- MANE Select
- NM_181882
- Type
- Deletion
- Location
- chr19:40396591 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 588
- 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 p.Ala210fs Pathogenic ★★ same condition
- PRX p.Asp765fs Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Ile1096fs Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Lys930fs Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Thr1033fs Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Val525fs Pathogenic/Likely pathogenic ★★ same condition
- PRX p.629MKLPE[1] Uncertain significance ★★ same condition
- PRX p.Ala1447fs Uncertain significance ★★ 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-pro588fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown