OPTN p.Ala481=
c.1443G>A · rs370287061 · VCV2042497
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, 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 -1.2 | GERP -3.8 |
| Overall | ||
| CADD | 4.297 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
Admixed American · 27/59,984 alleles
Filtering AF
0.0317%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0273%
Overall
0.00211%
34/1,613,352 alleles · ultra-rare
exomes 33/1,461,230 · genomes 1/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.045% | 2,222 |
| Middle Eastern | 0.0165% | 6,074 |
| East Asian | 0.00223% | 44,872 |
| African / African-American | 0.00134% | 74,854 |
| European (non-Finnish) | 0.000339% | 294,901 |
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.Ala481=
- Coding
- c.1443G>A
- MANE Select
- NM_001008212
- dbSNP
- rs370287061
- Type
- single nucleotide variant
- Location
- chr10:13132108 (GRCh38)
- Gene constraint
- LOEUF 0.877 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.90 · 14 PDB
- Residue 481
- an α-helix; the 'interaction with hd' region; the 'interaction with myo6' region
Similar variants
- OPTN p.Ala481Val Uncertain significance ★★ ⚠ same residue
- OPTN p.Ala481Thr 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
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-ala481 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown