Is OTOA p.Asp342Val (c.1025A>T) pathogenic?

OTOA p.Asp342Val (c.1025A>T) is classified Likely pathogenic in OTOA (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-27). AlphaMissense: ambiguous (0.4007); Ultra-rare (popmax 0.0165%, mid); Associated with autosomal recessive nonsyndromic hearing loss 1A.

What condition is associated with OTOA p.Asp342Val (c.1025A>T)?

OTOA p.Asp342Val (c.1025A>T) is associated with autosomal recessive nonsyndromic hearing loss 1A, autosomal recessive nonsyndromic hearing loss 22 (ClinVar).

How common is OTOA p.Asp342Val (c.1025A>T) in the general population?

OTOA p.Asp342Val (c.1025A>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about OTOA p.Asp342Val (c.1025A>T)?

AlphaMissense predicts ambiguous (score 0.4007) — an in-silico prediction, not a clinical call.

OTOA p.Asp342Val

c.1025A>T · rs1060499804 · VCV402269

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4007 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

autosomal recessive nonsyndromic hearing loss 1A

Computational evidence

Protein change
AlphaMissense	0.4007	ambiguous
REVEL	0.453	indeterminate
SaProt	LLR -11.12	damaging
Splicing
SpliceAI	Δ0.34	acceptor loss, 44 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 52 kb · p 0.02 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D356V vs ClinVar D342V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Overall 6.2e-05% 1/1,614,132 alleles · ultra-rare exomes 1/1,461,884 · genomes 0/152,248 · joint denominator

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.Asp342Val
Coding: c.1025A>T
MANE Select: NM_144672
dbSNP: rs1060499804
Type: single nucleotide variant
Location: chr16:21705213 (GRCh38)
Gene constraint: LOEUF 0.822 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.12

Full OTOA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 22

Similar variants

OTOA p.Asp342Glu Uncertain significance ★ ⚠ same residue
OTOA p.Asp342His Uncertain significance ★ ⚠ same residue
OTOA c.1320+2T>C Pathogenic ★★ same condition
OTOA c.1880+1G>A Pathogenic/Likely pathogenic ★★ same condition
OTOA c.399+2T>C Pathogenic/Likely pathogenic ★★ same condition
OTOA c.635+2T>A Pathogenic/Likely pathogenic ★★ same condition
OTOA p.Ser269Ter Pathogenic/Likely pathogenic ★★ same condition
OTOA p.Ala607Val Uncertain significance ★★ ⚠ same condition

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-asp342val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown