Is OPA1 p.Pro547fs (c.1640del) pathogenic?

OPA1 p.Pro547fs (c.1640del) is classified Likely pathogenic in OPA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). Associated with Behr syndrome.

What condition is associated with OPA1 p.Pro547fs (c.1640del)?

OPA1 p.Pro547fs (c.1640del) is associated with Behr syndrome (ClinVar).

OPA1 p.Pro547fs

c.1640del · VCV4795203

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Behr syndrome

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 17 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1

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

Variant & gene context

Gene: OPA1
Protein: p.Pro547fs
Coding: c.1640del
MANE Select: NM_130837
Type: Deletion
Location: chr3:193645582 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 74.02 · 11 PDB
Residue 547: an α-helix; the dynamin-type g domain

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

Disease context

Behr syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OPA1 c.2873_2876del Pathogenic/Likely pathogenic ★★ same condition
OPA1 c.2885_2983+8del Pathogenic/Likely pathogenic ★★ same condition
OPA1 p.Ser763fs Pathogenic ★★ same condition
OPA1 p.Lys979fs Likely pathogenic ★ same condition
OPA1 p.Arg38_Ser43del Conflicting classifications of pathogenicity ★ same condition
OPA1 p.Pro547Thr Uncertain significance ★ ⚠ same residue
OPA1 p.Pro547= Likely benign ★ same residue
OPA1 c.1935+1G>T Likely 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-pro547fs (accessed [today's date]).

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