Is OPA1 p.Arg682fs (c.2046_2047del) pathogenic?

OPA1 p.Arg682fs (c.20462047del) is classified Pathogenic in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). No gnomAD frequency available for this variant.

How common is OPA1 p.Arg682fs (c.2046_2047del) in the general population?

OPA1 p.Arg682fs (c.2046_2047del) is no gnomAD frequency available for this variant (gnomAD).

OPA1 p.Arg682fs

c.2046_2047del · rs2475017130 · VCV1810660

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 22 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.1, phastCons 1

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

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: OPA1
Protein: p.Arg682fs
Coding: c.2046_2047del
MANE Select: NM_130837
dbSNP: rs2475017130
Type: Microsatellite
Location: chr3:193654893 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 682: the 'stalk region' region

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

Similar variants

OPA1 p.Arg682Lys Uncertain significance ★★ ⚠ same residue
OPA1 p.Arg682Gly Uncertain significance ★ ⚠ same residue
OPA1 p.Arg682Ser Uncertain significance ★ ⚠ same residue
OPA1 p.Ile320fs Pathogenic ★★ same type
OPA1 p.Leu330_Ser331insTer Pathogenic/Likely pathogenic ★★ same type
OPA1 p.Lys269fs Pathogenic ★★ same type
OPA1 p.Thr469fs Pathogenic ★★ same type
OPA1 p.Val349del Pathogenic ★★ same type

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-arg682fs (accessed [today's date]).

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