OTOGL p.Ser2003=
c.6009C>T · rs773794520 · VCV1198265
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.013%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.026 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.12 | GERP -3.4, phastCons 0.97 |
| Overall | ||
| CADD | 4.736 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.013%
European (non-Finnish) · 151/1,163,946 alleles
Filtering AF
0.0113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00998%
158/1,583,016 alleles · ultra-rare
exomes 154/1,431,436 · genomes 4/151,580 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.013% | 7,708 |
| Remaining individualsnot grpmax-eligible | 0.00982% | 10,183 |
| African / African-American | 0.00136% | 73,294 |
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.Ser2003=
- Coding
- c.6009C>T
- MANE Select
- NM_001378609
- dbSNP
- rs773794520
- Type
- single nucleotide variant
- Location
- chr12:80356904 (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 c.1441+2T>C Pathogenic/Likely pathogenic ★★ same type
- OTOGL c.1890-1G>T Likely pathogenic ★★ same type
- OTOGL c.3213+1G>A Likely pathogenic ★★ same type
- OTOGL c.3635-2A>G Likely pathogenic ★★ same type
- OTOGL p.Arg1425Ter Pathogenic/Likely pathogenic ★★ same type
- OTOGL p.Arg1515Ter Pathogenic/Likely pathogenic ★★ same type
- OTOGL p.Arg1672Ter Pathogenic/Likely pathogenic ★★ same type
- OTOGL p.Arg1817Ter Pathogenic/Likely 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/otogl-p-ser2003 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown