OPA1 p.Lys874=
c.2622G>A · rs377280422 · VCV2086166
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 5.9 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 11.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
Admixed American · 12/59,990 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00898%
Overall
0.0018%
29/1,613,576 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.02% | 4,999 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,235 |
| European (non-Finnish) | 0.00119% | 84,262 |
| South Asian | 0.0011% | 91,072 |
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.Lys874=
- Coding
- c.2622G>A
- MANE Select
- NM_130837
- dbSNP
- rs377280422
- Type
- single nucleotide variant
- Location
- chr3:193662923 (GRCh38)
- Gene constraint
- LOEUF 0.503 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 74.02 · 11 PDB
- Residue 874
- the 'stalk region' region; a disulfide bond
Similar variants
- OPA1 p.Lys874Glu 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-lys874 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown