PRX p.Leu59Val
c.175C>G · VCV4628550
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3755 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3755 | ambiguous |
|---|---|---|
| REVEL | 0.192 | benign-leaning |
| SaProt | LLR -7.33 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.58 | GERP -2.3, phastCons 0.99 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 11 kb · p 0.97 · regional, not allelic |
| Overall | ||
| CADD | 22.9 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PRX
- Protein
- p.Leu59Val
- Coding
- c.175C>G
- MANE Select
- NM_181882
- Type
- single nucleotide variant
- Location
- chr19:40403715 (GRCh38)
- Gene constraint
- LOEUF 1.321 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 35.74 · 1 PDB
- Residue 59
- the pdz domain
Similar variants
- PRX p.Leu59Pro Uncertain significance ★ ⚠ same residue
- PRX c.184+2T>C Likely pathogenic ★★ same condition
- PRX p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Cys715Ter Pathogenic/Likely pathogenic ★★ same condition
- PRX p.Tyr77Ter Pathogenic ★★ same condition
- PRX p.Ala1036Val Uncertain significance ★★ ⚠ same condition
- PRX p.Ala1074Thr Uncertain significance ★★ ⚠ same condition
- PRX p.Ala1289Asp 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-leu59val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown