OPA1 p.Arg286=
c.856A>C · VCV4765594
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.096 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.3 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,524 alleles
Filtering AF
0.000775%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000614%
Overall
0.001%
16/1,594,470 alleles · very rare
exomes 13/1,442,254 · genomes 3/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,524 |
| European (non-Finnish) | 0.00129% | 77,505 |
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.Arg286=
- Coding
- c.856A>C
- MANE Select
- NM_130837
- Type
- single nucleotide variant
- Location
- chr3:193635430 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 74.02 · 11 PDB
- Residue 286
- the dynamin-type g domain
Similar variants
- OPA1 p.Arg286Ser Uncertain significance ★ ⚠ same residue
- OPA1 p.Arg286fs Likely pathogenic ★ same residue
- OPA1 c.1035+1G>A Pathogenic ★★ same type
- OPA1 c.1035+5G>A Pathogenic/Likely pathogenic ★★ same type
- OPA1 c.1149+1G>A Pathogenic ★★ same type
- OPA1 c.1149+1G>T Likely pathogenic ★★ same type
- OPA1 c.1150-2A>G Pathogenic ★★ same type
- OPA1 c.1230+1G>A 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-arg286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown