Is OPLAH p.Ala960= (c.2880T>G) pathogenic?

OPLAH p.Ala960= (c.2880T>G) is classified Likely benign in OPLAH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). Rare (popmax 0.15%, afr); Associated with 5-oxoprolinase deficiency.

What condition is associated with OPLAH p.Ala960= (c.2880T>G)?

OPLAH p.Ala960= (c.2880T>G) is associated with 5-oxoprolinase deficiency (ClinVar).

How common is OPLAH p.Ala960= (c.2880T>G) in the general population?

OPLAH p.Ala960= (c.2880T>G) is rare (popmax 0.15%, afr) (gnomAD).

How is 5-oxoprolinase deficiency inherited?

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

OPLAH p.Ala960=

c.2880T>G · rs372144482 · VCV1144331

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.15%, afr)

Conditions

5-oxoprolinase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.5	GERP -3.2
Overall
CADD	0.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.15% African / African-American · 112/74,854 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.119%

Overall 0.00803% 129/1,606,982 alleles · rare exomes 63/1,454,768 · genomes 66/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.15%	668
Admixed American	0.00846%	11,816
Remaining individualsnot grpmax-eligible	0.00643%	15,563
East Asian	0.00225%	44,512
European (non-Finnish)	0.000595%	168,190

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.Ala960=
Coding: c.2880T>G
MANE Select: NM_017570
dbSNP: rs372144482
Type: single nucleotide variant
Location: chr8:144053121 (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-ala960 (accessed [today's date]).

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