OTOA p.Ser471=
c.1413G>A · rs779657494 · VCV2715920
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0445%, eas)
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 0.053 | GERP -3.2 |
| Overall | ||
| CADD | 6.562 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0445%
East Asian · 20/44,902 alleles
Filtering AF
0.0295%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0246%
Overall
0.00477%
77/1,614,090 alleles · ultra-rare
exomes 69/1,461,878 · genomes 8/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0445% | 2,245 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00432% | 23,138 |
| Admixed American | 0.00333% | 30,001 |
| Finnishnot grpmax-eligible | 0.00156% | 64,038 |
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.Ser471=
- Coding
- c.1413G>A
- MANE Select
- NM_144672
- dbSNP
- rs779657494
- Type
- single nucleotide variant
- Location
- chr16:21715077 (GRCh38)
- Gene constraint
- LOEUF 0.822 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.12
Similar variants
- OTOA p.Ser471Leu 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
- 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-ser471 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown