Is PRODH p.Ser391= (c.1173C>T) pathogenic?

PRODH p.Ser391= (c.1173C>T) is classified Likely benign in PRODH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.19%, afr); Associated with hyperprolinemia type 1.

What condition is associated with PRODH p.Ser391= (c.1173C>T)?

PRODH p.Ser391= (c.1173C>T) is associated with hyperprolinemia type 1 (ClinVar).

How common is PRODH p.Ser391= (c.1173C>T) in the general population?

PRODH p.Ser391= (c.1173C>T) is low-frequency (popmax 3.19%, afr) (gnomAD).

How is Hyperprolinemia type 1 inherited?

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

PRODH p.Ser391=

c.1173C>T · rs3970556 · VCV697519

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.19%, afr)

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 5.1	GERP 2.5, phastCons 1
Overall
CADD	9.938	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.19% African / African-American · 104/3,256 alleles

Filtering AF 2.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.51%

Overall 0.402% 212/52,710 alleles · low-frequency exomes 172/48,190 · genomes 40/4,520 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.19%	31
Middle Eastern	1.1%	91
Remaining individualsnot grpmax-eligible	0.565%	177
East Asian	0.392%	255
Admixed American	0.391%	256
Ashkenazi Jewishnot grpmax-eligible	0.139%	719
European (non-Finnish)	0.119%	839
South Asian	0.0753%	1,328

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRODH
Protein: p.Ser391=
Coding: c.1173C>T
MANE Select: NM_016335
dbSNP: rs3970556
Type: single nucleotide variant
Location: chr22:18919529 (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 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
PRODH p.Ala140Thr 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-ser391 (accessed [today's date]).

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