OTOA p.Ala40=
c.120G>A · VCV3602960
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.43 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.44 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.29 | GERP -3.8, phastCons 0.008 |
| Overall | ||
| CADD | 19.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,866 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00118%
19/1,613,718 alleles · very rare
exomes 19/1,461,498 · genomes 0/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,433 |
| South Asian | 0.00439% | 22,771 |
| Admixed American | 0.00333% | 30,003 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| African / African-American | 0.00133% | 75,006 |
| European (non-Finnish) | 0.000763% | 131,101 |
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.Ala40=
- Coding
- c.120G>A
- MANE Select
- NM_144672
- Type
- single nucleotide variant
- Location
- chr16:21678943 (GRCh38)
- Gene constraint
- LOEUF 0.822 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.12
Similar variants
- OTOA p.Ala40Val 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-ala40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown