Is PRODH p.Ile14= (c.42T>C) pathogenic?

PRODH p.Ile14= (c.42T>C) is classified Likely benign in PRODH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). No allele count reported in gnomAD v4.1 (AN 8); Associated with hyperprolinemia type 1.

What condition is associated with PRODH p.Ile14= (c.42T>C)?

PRODH p.Ile14= (c.42T>C) is associated with hyperprolinemia type 1 (ClinVar).

How common is PRODH p.Ile14= (c.42T>C) in the general population?

PRODH p.Ile14= (c.42T>C) is no allele count reported in gnomAD v4.1 (AN 8) (gnomAD).

How is Hyperprolinemia type 1 inherited?

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

PRODH p.Ile14=

c.42T>C · rs761010757 · VCV459916

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 8)

Conditions

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 -0.69	GERP -1.9
Overall
CADD	5.426	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 8). 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.Ile14=
Coding: c.42T>C
MANE Select: NM_016335
dbSNP: rs761010757
Type: single nucleotide variant
Location: chr22:18936246 (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.Ile14Thr 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-ile14 (accessed [today's date]).

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