OTOA p.Ser391=
c.1173G>A · rs143326637 · VCV286963
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0949%, afr)
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 -10 | GERP -3.2 |
| Overall | ||
| CADD | 0.211 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0949%
African / African-American · 71/74,854 alleles
Filtering AF
0.0771%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0706%
Overall
0.00564%
91/1,613,806 alleles · ultra-rare
exomes 35/1,461,816 · genomes 56/151,990 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0949% | 1,054 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,596 |
| Admixed American | 0.00333% | 29,988 |
| East Asian | 0.00223% | 44,878 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000932% | 107,266 |
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.Ser391=
- Coding
- c.1173G>A
- MANE Select
- NM_144672
- dbSNP
- rs143326637
- Type
- single nucleotide variant
- Location
- chr16:21709956 (GRCh38)
- Gene constraint
- LOEUF 0.822 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.12
Similar variants
- OTOA p.Ser391Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- OTOA p.Ser391Thr Uncertain significance ★ ⚠ same residue
- 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
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-ser391 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown