OPTN p.Pro292=
c.876G>A · rs151065414 · VCV1611830
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.348%, afr)
Conditions
2
OPTN-related open angle glaucoma
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.025 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.72 | GERP -5.2, phastCons 0.005 |
| Overall | ||
| CADD | 6.139 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.348%
African / African-American · 261/74,962 alleles
Filtering AF
0.313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.3%
Overall
0.0236%
380/1,610,656 alleles · rare
exomes 213/1,458,424 · genomes 167/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.348% | 287 |
| Remaining individualsnot grpmax-eligible | 0.0465% | 2,152 |
| Admixed American | 0.02% | 5,000 |
| Middle Eastern | 0.0165% | 6,056 |
| South Asian | 0.0121% | 8,275 |
| European (non-Finnish) | 0.00552% | 18,105 |
| East Asian | 0.00223% | 44,856 |
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.Pro292=
- Coding
- c.876G>A
- MANE Select
- NM_001008212
- dbSNP
- rs151065414
- Type
- single nucleotide variant
- Location
- chr10:13122481 (GRCh38)
- Gene constraint
- LOEUF 0.877 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.90 · 14 PDB
- Residue 292
- the 'disordered' region
Similar variants
- OPTN p.Pro292Leu Uncertain significance ★★ ⚠ same residue
- 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
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-pro292 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown