Is OPA3 p.Ala5fs (c.13_20del) pathogenic?

OPA3 p.Ala5fs (c.1320del) is classified Likely pathogenic in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). Associated with 3-methylglutaconic aciduria type 3.

What condition is associated with OPA3 p.Ala5fs (c.13_20del)?

OPA3 p.Ala5fs (c.13_20del) is associated with 3-methylglutaconic aciduria type 3 (ClinVar).

How is 3-methylglutaconic aciduria type 3 inherited?

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

OPA3 p.Ala5fs

c.13_20del · VCV4816243

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

3-methylglutaconic aciduria type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.028	GERP -4.3, phastCons 0.11

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: OPA3
Protein: p.Ala5fs
Coding: c.13_20del
MANE Select: NM_025136
Type: Deletion
Location: chr19:45584745 (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.Ala5Thr Uncertain significance ★ ⚠ same residue
OPA3 p.Ala5= Likely benign ★ same residue
OPA3 p.Gly65fs Likely pathogenic ★★ same condition
OPA3 p.Leu149fs Uncertain significance ★★ 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

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-ala5fs (accessed [today's date]).

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