OPA1 p.Glu435=
c.1305G>A · rs2474865823 · VCV2203478
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
optic atrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Pangolin | Δ0.24 | loss · gain 0.02 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.7 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- OPA1
- Protein
- p.Glu435=
- Coding
- c.1305G>A
- MANE Select
- NM_130837
- dbSNP
- rs2474865823
- Type
- single nucleotide variant
- Location
- chr3:193643049 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 74.02 · 11 PDB
- Residue 435
- a β-strand; the dynamin-type g domain
Similar variants
- OPA1 c.1230+1G>A Pathogenic ★★ same condition
- OPA1 c.1935+1G>C Pathogenic/Likely pathogenic ★★ same condition
- OPA1 c.2779-9A>G Pathogenic/Likely pathogenic ★★ same condition
- OPA1 c.949-1G>A Pathogenic ★★ same condition
- OPA1 p.Arg290Ter Pathogenic ★★ same condition
- OPA1 p.Arg367Ter Pathogenic ★★ same condition
- OPA1 p.Arg38Ter Pathogenic ★★ same condition
- OPA1 p.Arg421Ter 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-glu435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown