Is PRODH p.Leu366Pro (c.1097T>C) pathogenic?

PRODH p.Leu366Pro (c.1097T>C) is classified Uncertain significance in PRODH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). No allele count reported in gnomAD v4.1 (AN 11,998); Associated with schizophrenia 4.

What condition is associated with PRODH p.Leu366Pro (c.1097T>C)?

PRODH p.Leu366Pro (c.1097T>C) is associated with schizophrenia 4 (ClinVar).

How common is PRODH p.Leu366Pro (c.1097T>C) in the general population?

PRODH p.Leu366Pro (c.1097T>C) is no allele count reported in gnomAD v4.1 (AN 11,998) (gnomAD).

PRODH p.Leu366Pro

c.1097T>C · VCV4879488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 11,998)

Conditions

schizophrenia 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.716	pathogenic-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 4.6, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 23 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 11,998). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRODH
Protein: p.Leu366Pro
Coding: c.1097T>C
MANE Select: NM_016335
Type: single nucleotide variant
Location: chr22:18919713 (GRCh38)
Structure: AlphaFold pLDDT 85.29

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

Disease context

schizophrenia 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRODH p.Leu366= Likely benign ★ same residue
PRODH c.1104+2T>C Likely pathogenic ★★ same condition
PRODH p.Gln59Ter Pathogenic/Likely 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
PRODH p.Ala268Val 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-leu366pro (accessed [today's date]).

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