OPTN p.Ser171=
c.513C>T · rs369760173 · VCV1543842
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0185%, nfe)
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 -20 | GERP -4.8 |
| Overall | ||
| CADD | 0.133 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0185%
European (non-Finnish) · 218/1,180,040 alleles
Filtering AF
0.0165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0157%
Overall
0.0145%
234/1,614,048 alleles · ultra-rare
exomes 231/1,461,890 · genomes 3/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0185% | 5,413 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| African / African-American | 0.004% | 24,970 |
| Admixed American | 0.00167% | 59,996 |
| South Asian | 0.0011% | 91,088 |
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.Ser171=
- Coding
- c.513C>T
- MANE Select
- NM_001008212
- dbSNP
- rs369760173
- Type
- single nucleotide variant
- Location
- chr10:13112596 (GRCh38)
- Gene constraint
- LOEUF 0.877 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.90 · 14 PDB
- Residue 171
- the 'interaction with rab8' region
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-ser171 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown