Is OPA1 p.Arg101fs (c.295_301dup) pathogenic?

OPA1 p.Arg101fs (c.295301dup) is classified Pathogenic in OPA1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-01-01). Associated with optic atrophy.

What condition is associated with OPA1 p.Arg101fs (c.295_301dup)?

OPA1 p.Arg101fs (c.295_301dup) is associated with optic atrophy (ClinVar).

OPA1 p.Arg101fs

c.295_301dup · VCV3250166

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

optic atrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.42	GERP 0.38, phastCons 0.74

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

Variant & gene context

Gene: OPA1
Protein: p.Arg101fs
Coding: c.295_301dup
MANE Select: NM_130837
Type: Duplication
Location: chr3:193614984 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB

Full OPA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

optic atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OPA1 c.1377+2dup Pathogenic ★★ same condition
OPA1 c.2441-4dup Conflicting classifications of pathogenicity ★ same condition
OPA1 p.Arg101Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
OPA1 p.Arg101His Conflicting classifications of pathogenicity ★ ⚠ same residue
OPA1 p.Arg101Leu Uncertain significance ★ ⚠ same residue
OPA1 p.Arg101Ser Uncertain significance ★ ⚠ same residue
OPA1 c.2439_2440+3dup Likely pathogenic same condition
OPA1 c.(843+1_844-1 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/opa1-p-arg101fs (accessed [today's date]).

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