OPA1 p.Gln677=
c.2031A>G · rs1283596761 · VCV1664716
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
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 -0.85 | GERP -4.5 |
| Overall | ||
| CADD | 2.581 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,994 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000496%
8/1,613,766 alleles · very rare
exomes 7/1,461,552 · genomes 1/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,997 |
| South Asian | 0.00329% | 30,361 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
| African / African-American | 0.00134% | 74,904 |
| European (non-Finnish) | 8.48e-05% | 1,179,924 |
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.Gln677=
- Coding
- c.2031A>G
- MANE Select
- NM_130837
- dbSNP
- rs1283596761
- Type
- single nucleotide variant
- Location
- chr3:193654880 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 74.02 · 11 PDB
- Residue 677
- the 'stalk region' region
Similar variants
- OPA1 p.Gln677Arg Uncertain significance ★ ⚠ 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
- OPA1 c.1230+5G>A Pathogenic/Likely 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-gln677 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown