Is PRODH p.Ser162= (c.486C>G) pathogenic?

PRODH p.Ser162= (c.486C>G) is classified Likely benign in PRODH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0106%, nfe); Associated with hyperprolinemia type 1.

What condition is associated with PRODH p.Ser162= (c.486C>G)?

PRODH p.Ser162= (c.486C>G) is associated with hyperprolinemia type 1 (ClinVar).

How common is PRODH p.Ser162= (c.486C>G) in the general population?

PRODH p.Ser162= (c.486C>G) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

How is Hyperprolinemia type 1 inherited?

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

PRODH p.Ser162=

c.486C>G · rs146472255 · VCV2077640

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Conditions

hyperprolinemia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP 1.4, phastCons 1
Overall
CADD	6.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% European (non-Finnish) · 2/18,826 alleles

Filtering AF 0.00186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000756%

Overall 0.00526% 2/38,022 alleles · ultra-rare exomes 2/36,500 · genomes 0/1,522 · joint denominator

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.Ser162=
Coding: c.486C>G
MANE Select: NM_016335
dbSNP: rs146472255
Type: single nucleotide variant
Location: chr22:18925719 (GRCh38)
Structure: AlphaFold pLDDT 85.29
Residue 162: the 'disordered' region

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.Ser162Tyr Uncertain significance ★ same residue
PRODH p.Ser162Phe 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

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-ser162 (accessed [today's date]).

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