OTOGL p.Ser2129Pro
c.6385T>C · rs374792814 · VCV2196865
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0138%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.257 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 11 kb · p 0.37 · regional, not allelic |
| Overall | ||
| CADD | 23.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0138%
African / African-American · 10/72,436 alleles
Filtering AF
0.00746%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00567%
Overall
0.000711%
11/1,546,162 alleles · ultra-rare
exomes 6/1,394,048 · genomes 5/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0138% | 7,244 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,930 |
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
- OTOGL
- Protein
- p.Ser2129Pro
- Coding
- c.6385T>C
- MANE Select
- NM_001378609
- dbSNP
- rs374792814
- Type
- single nucleotide variant
- Location
- chr12:80367614 (GRCh38)
- Gene constraint
- LOEUF 1.069 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 72.19
Similar variants
- OTOGL p.Ser2129Cys Uncertain significance ★★ same residue
- OTOGL c.3213+1G>A Likely pathogenic ★★ same condition
- OTOGL p.Arg1515Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOGL p.Trp647Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOGL p.Ala1270Glu Uncertain significance ★★ same condition
- OTOGL p.Ala1299Val Uncertain significance ★★ same condition
- OTOGL p.Ala280Thr Uncertain significance ★★ same condition
- OTOGL p.Ala644Thr 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/otogl-p-ser2129pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown