Is OPA3 p.Phe90del (c.268_270del) pathogenic?

OPA3 p.Phe90del (c.268270del) is classified Uncertain significance in OPA3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-05-07). Very rare (popmax 8.47e-05%, nfe); Associated with 3-methylglutaconic aciduria type 3.

What condition is associated with OPA3 p.Phe90del (c.268_270del)?

OPA3 p.Phe90del (c.268_270del) is associated with 3-methylglutaconic aciduria type 3 (ClinVar).

How common is OPA3 p.Phe90del (c.268_270del) in the general population?

OPA3 p.Phe90del (c.268_270del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is 3-methylglutaconic aciduria type 3 inherited?

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

OPA3 p.Phe90del

c.268_270del · rs755084544 · VCV558222

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

3-methylglutaconic aciduria type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -13	GERP -3.3

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,174 alleles · very rare exomes 1/1,461,834 · genomes 0/152,340 · 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: OPA3
Protein: p.Phe90del
Coding: c.268_270del
MANE Select: NM_025136 · reported on NM_001017989
dbSNP: rs755084544
Type: Deletion
Location: chr19:45529329 (GRCh38)
Gene constraint: LOEUF 1.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.13

Full OPA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3-methylglutaconic aciduria type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 3-methylglutaconic aciduria type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

OPA3 p.Gly65fs Likely pathogenic ★★ same condition
OPA3 p.Leu149fs Uncertain significance ★★ same condition
OPA3 p.Ala5fs Likely pathogenic ★ same condition
OPA3 p.Arg103fs Likely pathogenic ★ same condition
OPA3 p.Cys96fs Likely pathogenic ★ same condition
OPA3 p.Glu158fs Likely pathogenic ★ same condition
OPA3 p.Val19fs Pathogenic ★ same condition
OPA3 c.142+3_142+6del 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/opa3-p-phe90del (accessed [today's date]).

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