Is OPA3 p.Arg123Pro (c.368_369delinsCT) pathogenic?

OPA3 p.Arg123Pro (c.368369delinsCT) is classified Uncertain significance in OPA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). No gnomAD frequency available for this variant; Associated with 3-methylglutaconic aciduria type 3.

What condition is associated with OPA3 p.Arg123Pro (c.368_369delinsCT)?

OPA3 p.Arg123Pro (c.368_369delinsCT) is associated with 3-methylglutaconic aciduria type 3, optic atrophy 3 (ClinVar).

How common is OPA3 p.Arg123Pro (c.368_369delinsCT) in the general population?

OPA3 p.Arg123Pro (c.368_369delinsCT) is no gnomAD frequency available for this variant (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.Arg123Pro

c.368_369delinsCT · rs2513823863 · VCV2943231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.19 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OPA3
Protein: p.Arg123Pro
Coding: c.368_369delinsCT
MANE Select: NM_025136
dbSNP: rs2513823863
Type: Indel
Location: chr19:45553685 (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

Also linked: optic atrophy 3

For 3-methylglutaconic aciduria type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

OPA3 p.Arg123Trp Uncertain significance ★★ ⚠ same residue
OPA3 p.Arg123= Likely benign ★ same residue
OPA3 c.143-2_143-1delinsCC Pathogenic ★ same condition
OPA3 p.Gln137fs Likely pathogenic ★ same condition
OPA3 p.Ile27_Lys28insTer Likely pathogenic ★ same condition
OPA3 p.Gln141_Ala142delinsHisSer Uncertain significance ★ same condition
OPA3 p.Glu179fs Uncertain significance ★ same condition
OPA3 p.Pro144Thr 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-arg123pro (accessed [today's date]).

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