OPA1 p.Ala246=
c.738G>A · rs775388791 · VCV1575534
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -3.1 |
| Overall | ||
| CADD | 6.346 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,080 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.0031%
50/1,613,988 alleles · very rare
exomes 49/1,461,836 · genomes 1/152,152 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,216 |
| European (non-Finnish) | 0.00356% | 28,095 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
| African / African-American | 0.00134% | 74,906 |
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.Ala246=
- Coding
- c.738G>A
- MANE Select
- NM_130837
- dbSNP
- rs775388791
- Type
- single nucleotide variant
- Location
- chr3:193626151 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 74.02 · 11 PDB
Similar variants
- OPA1 p.Ala246Gly Uncertain significance ★ same residue
- OPA1 p.Ala246Val Conflicting classifications of pathogenicity ★ 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-ala246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown