OTX2 p.Ala99=
c.297T>C · rs2139529344 · VCV1532264
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
Anophthalmia-microphthalmia syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP -2.3, phastCons 0.5 |
| Overall | ||
| CADD | 8.332 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,084 alleles
Overall
6.84e-05%
1/1,461,878 alleles · very rare
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
- OTX2
- Protein
- p.Ala99=
- Coding
- c.297T>C
- MANE Select
- NM_021728
- dbSNP
- rs2139529344
- Type
- single nucleotide variant
- Location
- chr14:56802332 (GRCh38)
- Gene constraint
- LOEUF 0.324 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99
- Residue 99
- the 'disordered' region
Similar variants
- OTX2 p.Ala99Asp Pathogenic same residue
- OTX2 p.Arg76Ter Pathogenic ★★ same condition
- OTX2 p.Ser211Ter Pathogenic/Likely pathogenic ★★ same condition
- OTX2 p.Ala234Val Uncertain significance ★★ ⚠ same condition
- OTX2 p.Arg102His Uncertain significance ★★ ⚠ same condition
- OTX2 p.Arg48Trp Uncertain significance ★★ ⚠ same condition
- OTX2 p.Leu64Met Uncertain significance ★★ ⚠ same condition
- OTX2 p.Lys95Glu Uncertain significance ★★ ⚠ 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/otx2-p-ala99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown