Is OPLAH p.Pro224= (c.672C>T) pathogenic?

OPLAH p.Pro224= (c.672C>T) is classified Likely benign in OPLAH (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-24). Ultra-rare (popmax 0.011%, sas); Associated with 5-oxoprolinase deficiency.

What condition is associated with OPLAH p.Pro224= (c.672C>T)?

OPLAH p.Pro224= (c.672C>T) is associated with 5-oxoprolinase deficiency (ClinVar).

How common is OPLAH p.Pro224= (c.672C>T) in the general population?

OPLAH p.Pro224= (c.672C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

How is 5-oxoprolinase deficiency inherited?

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

OPLAH p.Pro224=

c.672C>T · rs368105559 · VCV1084729

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

5-oxoprolinase deficiency

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 -1.1	GERP -3
Overall
CADD	7.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/90,984 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00454%

Overall 0.000873% 14/1,603,424 alleles · ultra-rare exomes 11/1,451,102 · genomes 3/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,098
East Asian	0.00446%	22,430
Remaining individualsnot grpmax-eligible	0.0016%	62,370
European (non-Finnish)	8.48e-05%	1,179,386

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: OPLAH
Protein: p.Pro224=
Coding: c.672C>T
MANE Select: NM_017570
dbSNP: rs368105559
Type: single nucleotide variant
Location: chr8:144058607 (GRCh38)
Gene constraint: LOEUF 1.163 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.08

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

Disease context

5-oxoprolinase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 5-oxoprolinase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

OPLAH c.587+1G>A Pathogenic/Likely pathogenic ★★ same condition
OPLAH p.Gln1006Ter Pathogenic/Likely pathogenic ★★ same condition
OPLAH p.Tyr248Ter Likely pathogenic ★★ same condition
OPLAH p.Ala1093Val Uncertain significance ★★ ⚠ same condition
OPLAH p.Ala344Thr Uncertain significance ★★ ⚠ same condition
OPLAH p.Ala422Val Uncertain significance ★★ ⚠ same condition
OPLAH p.Ala46Thr Uncertain significance ★★ ⚠ same condition
OPLAH p.Ala475Val 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/oplah-p-pro224 (accessed [today's date]).

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