# NM_144672.3(OTOA):c.(?_2302)_(2431_?)del

https://sugi.bio/variant/otoa-c-2302

## Summary

**OTOA c.(?_2302** is classified **Pathogenic** in OTOA (ClinVar, Single submitter, 1 submitter; last evaluated 2014-02-27). Associated with Rare genetic deafness.

**At a glance:** Pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the OTOA gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to Rare genetic deafness.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [OTOA](https://sugi.bio/atlas/gene/OTOA/) |
| Coding change (HGVS c.) | c.(?_2302 |
| MANE Select transcript | [NM_144672](https://www.ncbi.nlm.nih.gov/nuccore/NM_144672) |
| Variant type | Deletion |
| Location | chr16:None-None (GRCh38) |
| ClinVar | [VCV164814](https://www.ncbi.nlm.nih.gov/clinvar/variation/164814/) |

**All HGVS expressions:** `NC_000016.10:g.(?_21736261)_(21736390_?)del`, `NC_000016.9:g.(?_21747582)_(21747711_?)del`

## Gene constraint & dosage {#gene-context}

**OTOA** population constraint: LOEUF 0.822, pLI 8.5242e-16, missense-Z 1.398. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **nonsyndromic genetic hearing loss** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 84.12, 52% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of OTOA (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*


### Pathways affected {#pathways}

OTOA participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Post-translational modification: synthesis of GPI-anchored proteins](https://reactome.org/content/detail/R-HSA-163125) | other |

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2014-02-27.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Pathogenic | criteria provided, single submitter | clinical testing | 2014-02-27 |

## Associated conditions {#conditions}

[Rare genetic deafness](https://sugi.bio/atlas/disease/rare-genetic-deafness/).

**Reported phenotype names (ClinVar):** Rare genetic deafness.

## Similar variants {#similar}

Related OTOA variant pages (same residue, condition, or type): [OTOA p.His987fs](/variant/otoa-p-his987fs), [OTOA c.1880+1G>A](/variant/otoa-c-1880-plus-1g-a), [OTOA p.Ser249fs](/variant/otoa-p-ser249fs), [OTOA c.1688+1G>T](/variant/otoa-c-1688-plus-1g-t), [OTOA c.268-2A>G](/variant/otoa-c-268-minus-2a-g), [OTOA p.Arg699fs](/variant/otoa-p-arg699fs), [OTOA p.Gln589fs](/variant/otoa-p-gln589fs), [OTOA p.Ile701fs](/variant/otoa-p-ile701fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 164814). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*