OTOA p.Arg205=
c.615C>T · rs16972658 · VCV47955
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 6.81%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.9 | GERP -2.5 |
| Overall | ||
| CADD | 0.198 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.81%
Middle Eastern · 394/5,782 alleles
Filtering AF
6.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.04%
Overall
3.52%
56,753/1,611,076 alleles · common
exomes 51,649/1,460,578 · genomes 5,104/150,498 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 6.81% | 15 |
| European (non-Finnish) | 3.86% | 26 |
| Remaining individualsnot grpmax-eligible | 3.69% | 27 |
| Finnishnot grpmax-eligible | 3.57% | 28 |
| Admixed American | 3.11% | 32 |
| Ashkenazi Jewishnot grpmax-eligible | 2.99% | 33 |
| African / African-American | 2.91% | 34 |
| Amishnot grpmax-eligible | 1.87% | 53 |
| South Asian | 1.12% | 89 |
| East Asian | 0.733% | 136 |
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.Arg205=
- Coding
- c.615C>T
- MANE Select
- NM_144672
- dbSNP
- rs16972658
- Type
- single nucleotide variant
- Location
- chr16:21687628 (GRCh38)
- Gene constraint
- LOEUF 0.822 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.12
Similar variants
- OTOA p.Arg205Cys 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-arg205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown