PRODH p.Glu450Lys
c.1348G>A · VCV3587790
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
hyperprolinemia type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.643 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 4.3, phastCons 1 |
| Regional constraint | o/e 0.12 | constrained · MANE · 23 kb · p 1.7e-05 · regional, not allelic |
| Overall | ||
| CADD | 28.7 | PHRED · no single calibrated threshold — expert panels disagree |
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
- PRODH
- Protein
- p.Glu450Lys
- Coding
- c.1348G>A
- MANE Select
- NM_016335
- Type
- single nucleotide variant
- Location
- chr22:18918395 (GRCh38)
- Structure
- AlphaFold pLDDT 85.29
Disease context
hyperprolinemia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: schizophrenia 4
For Hyperprolinemia type 1 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
Similar variants
- PRODH p.Glu450Asp Uncertain significance ★ same residue
- PRODH p.Glu450Gly Uncertain significance ★ same residue
- PRODH c.1104+2T>C Likely pathogenic ★★ same condition
- PRODH p.Gln59Ter Pathogenic/Likely pathogenic ★★ same condition
- PRODH p.Tyr412Ter Pathogenic ★★ same condition
- PRODH c.1427+4C>T Uncertain significance ★★ same condition
- PRODH c.1615+1G>C Uncertain significance ★★ same condition
- PRODH c.482+6G>A 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/prodh-p-glu450lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown