OPTN p.His26=
c.78C>T · rs1588433321 · VCV756457
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
OPTN-related open angle glaucoma
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.57 | GERP -3.5 |
| Overall | ||
| CADD | 0.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,016 alleles
Overall
0.000124%
2/1,614,002 alleles · very rare
exomes 2/1,461,828 · genomes 0/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,016 |
| European (non-Finnish) | 8.47e-05% | 1,179,993 |
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
- OPTN
- Protein
- p.His26=
- Coding
- c.78C>T
- MANE Select
- NM_001008212
- dbSNP
- rs1588433321
- Type
- single nucleotide variant
- Location
- chr10:13109200 (GRCh38)
- Gene constraint
- LOEUF 0.877 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.90 · 14 PDB
- Residue 26
- the 'disordered' region; a UniProt-annotated variant site (in glc1e)
Similar variants
- OPTN c.1149-2A>G Likely pathogenic ★★ same condition
- OPTN c.626+1G>A Likely pathogenic ★★ same condition
- OPTN c.780-2A>C Likely pathogenic ★★ same condition
- OPTN p.Gln165Ter Pathogenic/Likely pathogenic ★★ same condition
- OPTN p.Gln335Ter Pathogenic ★★ same condition
- OPTN p.Gln79Ter Pathogenic/Likely pathogenic ★★ same condition
- OPTN p.Glu135Ter Pathogenic ★★ same condition
- OPTN p.Glu399Ter Pathogenic/Likely 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/optn-p-his26 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown