OTOA p.Phe191=
c.573T>C · rs746124082 · VCV2721213
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0362%, sas)
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 -2.2 | GERP -2.5 |
| Overall | ||
| CADD | 2.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0362%
South Asian · 33/91,048 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0231%
Overall
0.00211%
34/1,613,752 alleles · ultra-rare
exomes 34/1,461,882 · genomes 0/151,870 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0362% | 2,759 |
| East Asian | 0.00223% | 44,860 |
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.Phe191=
- Coding
- c.573T>C
- MANE Select
- NM_144672
- dbSNP
- rs746124082
- Type
- single nucleotide variant
- Location
- chr16:21687586 (GRCh38)
- Gene constraint
- LOEUF 0.822 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.12
Similar variants
- OTOA p.Phe191fs Pathogenic/Likely pathogenic ★★ 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
- OTOA p.Arg148Ter 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-phe191 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown