Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hyperprolinemia type 1
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 1.5 | GERP -3.2, phastCons 0.83 |
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.Trp185=
- Coding
- c.553=
- MANE Select
- NM_016335
- dbSNP
- rs4819756
- Type
- single nucleotide variant
- Location
- chr22:18925165 (GRCh38)
- Structure
- AlphaFold pLDDT 85.29
- Residue 185
- a UniProt-annotated variant site (increased proline dehydrogenase activity)
Disease context
hyperprolinemia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hyperprolinemia type 1 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
Similar variants
- PRODH p.Trp185Arg Benign ★★ same residue
- PRODH p.Trp185Ter Benign/Likely benign ★★ same residue
- PRODH p.Trp185Gln Benign ★ 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
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-trp185 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown