OPA1 p.Val452fs
c.1353_1354insACCA · VCV3250054
Likely pathogenic
No assertion criteria
Classification
Likely pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
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 14 of 31 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -2.1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- OPA1
- Protein
- p.Val452fs
- Coding
- c.1353_1354insACCA
- MANE Select
- NM_130837
- Type
- Insertion
- Location
- chr3:193643420 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 74.02 · 11 PDB
- Residue 452
- an α-helix; the dynamin-type g domain
Similar variants
- OPA1 p.Val452Gly Pathogenic same residue
- OPA1 c.1230+1G>A Pathogenic ★★ same condition
- OPA1 c.1377+2dup Pathogenic ★★ same condition
- OPA1 c.1935+1G>C Pathogenic/Likely pathogenic ★★ same condition
- OPA1 c.2012+4_2012+7del Pathogenic/Likely pathogenic ★★ same condition
- OPA1 c.2779-9A>G Pathogenic/Likely pathogenic ★★ same condition
- OPA1 c.2873_2876del Pathogenic/Likely pathogenic ★★ same condition
- OPA1 c.949-1G>A 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-val452fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown