OPTN p.Ala343=
c.1029A>T · rs1833437260 · VCV2640306
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 1.1 | GERP -0.67, phastCons 0.27 |
| Overall | ||
| CADD | 9.893 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,954 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000124%
2/1,614,072 alleles · very rare
exomes 1/1,461,828 · genomes 1/152,244 · joint denominator
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.Ala343=
- Coding
- c.1029A>T
- MANE Select
- NM_001008212
- dbSNP
- rs1833437260
- Type
- single nucleotide variant
- Location
- chr10:13125448 (GRCh38)
- Gene constraint
- LOEUF 0.877 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.90 · 14 PDB
Similar variants
- OPTN p.Ala343Ser Uncertain significance ★ ⚠ same residue
- OPTN c.1149-2A>G Likely pathogenic ★★ same type
- OPTN c.626+1G>A Likely pathogenic ★★ same type
- OPTN c.780-2A>C Likely pathogenic ★★ same type
- OPTN p.Gln165Ter Pathogenic/Likely pathogenic ★★ same type
- OPTN p.Gln335Ter Pathogenic ★★ same type
- OPTN p.Gln79Ter Pathogenic/Likely pathogenic ★★ same type
- OPTN p.Glu135Ter 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/optn-p-ala343 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown