Is PRODH p.Pro51Ser (c.151C>T) pathogenic?

PRODH p.Pro51Ser (c.151C>T) is classified Uncertain significance in PRODH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-11). Absent from gnomAD v4.1; Associated with hyperprolinemia type 1.

What condition is associated with PRODH p.Pro51Ser (c.151C>T)?

PRODH p.Pro51Ser (c.151C>T) is associated with hyperprolinemia type 1 (ClinVar).

How common is PRODH p.Pro51Ser (c.151C>T) in the general population?

PRODH p.Pro51Ser (c.151C>T) is absent from gnomAD v4.1 (gnomAD).

How is Hyperprolinemia type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRODH p.Pro51Ser

c.151C>T · rs2517463353 · VCV2124727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hyperprolinemia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.042	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 23 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	19.26	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.Pro51Ser
Coding: c.151C>T
MANE Select: NM_016335
dbSNP: rs2517463353
Type: single nucleotide variant
Location: chr22:18936137 (GRCh38)
Structure: AlphaFold pLDDT 85.29

Full PRODH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyperprolinemia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperprolinemia type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

PRODH p.Pro51Leu 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
PRODH c.929+3G>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-pro51ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown