OTOA p.Ser21=
c.63G>A · rs780990149 · VCV669024
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.40 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.77 | GERP -3.6 |
| Overall | ||
| CADD | 0.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
African / African-American · 5/74,820 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.00297%
48/1,613,730 alleles · very rare
exomes 43/1,461,776 · genomes 5/151,954 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00668% | 14,964 |
| European (non-Finnish) | 0.00347% | 28,780 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
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
- OTOA
- Protein
- p.Ser21=
- Coding
- c.63G>A
- MANE Select
- NM_144672
- dbSNP
- rs780990149
- Type
- single nucleotide variant
- Location
- chr16:21678577 (GRCh38)
- Gene constraint
- LOEUF 0.822 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.12
Similar variants
- OTOA c.1320+2T>C Pathogenic ★★ same type
- OTOA c.1880+1G>A Pathogenic/Likely pathogenic ★★ same type
- OTOA c.399+2T>C Pathogenic/Likely pathogenic ★★ same type
- OTOA c.635+2T>A Pathogenic/Likely pathogenic ★★ same type
- OTOA c.92-1G>T Pathogenic/Likely pathogenic ★★ same type
- OTOA p.Arg146Ter Pathogenic/Likely pathogenic ★★ same type
- OTOA p.Arg148Ter Pathogenic ★★ same type
- OTOA p.Lys667Glu 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/otoa-p-ser21 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown