Is OPA1 p.Asp266fs (c.796_799del) pathogenic?

OPA1 p.Asp266fs (c.796799del) is classified Pathogenic in OPA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-05-27). Very rare (popmax 0.0011%, sas); Associated with inherited retinal dystrophy.

What condition is associated with OPA1 p.Asp266fs (c.796_799del)?

OPA1 p.Asp266fs (c.796_799del) is associated with inherited retinal dystrophy, optic atrophy (ClinVar).

How common is OPA1 p.Asp266fs (c.796_799del) in the general population?

OPA1 p.Asp266fs (c.796_799del) is very rare (popmax 0.0011%, sas) (gnomAD).

OPA1 p.Asp266fs

c.796_799del · rs2474747856 · VCV2203473

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

inherited retinal dystrophy

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 8 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -2.2, phastCons 0.99

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,844 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000249% 4/1,607,792 alleles · very rare exomes 4/1,455,514 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,844
European (non-Finnish)	0.000255%	391,501

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: OPA1
Protein: p.Asp266fs
Coding: c.796_799del
MANE Select: NM_130837
dbSNP: rs2474747856
Type: Deletion
Location: chr3:193631616 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 266: an α-helix

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: optic atrophy

Similar variants

OPA1 c.2012+4_2012+7del Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2873_2876del Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.His686fs Pathogenic ★★ same condition
OPA1 p.Lys267fs Pathogenic ★★ same condition
OPA1 p.Val997fs Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Glu877fs Pathogenic ★ same condition
OPA1 c.611-8_611-3del Uncertain significance ★ same condition
OPA1 p.Arg38_Ser43del Conflicting classifications of pathogenicity ★ 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-asp266fs (accessed [today's date]).

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