Is OTOA p.Ser61Pro (c.181T>C) pathogenic?

OTOA p.Ser61Pro (c.181T>C) is classified Uncertain significance in OTOA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-12). AlphaMissense: likely benign (0.3169); Absent from gnomAD v4.1; Associated with hearing loss disorder.

What condition is associated with OTOA p.Ser61Pro (c.181T>C)?

OTOA p.Ser61Pro (c.181T>C) is associated with hearing loss disorder (ClinVar).

How common is OTOA p.Ser61Pro (c.181T>C) in the general population?

OTOA p.Ser61Pro (c.181T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OTOA p.Ser61Pro (c.181T>C)?

AlphaMissense predicts likely benign (score 0.3169) — an in-silico prediction, not a clinical call.

OTOA p.Ser61Pro

c.181T>C · rs369772866 · VCV812157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3169 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.3169	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -14.20	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79	GERP -2.2, phastCons 0.52
Regional constraint	o/e 0.92	unconstrained · MANE · 52 kb · p 0.02 · regional, not allelic
Overall
CADD	19.16	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OTOA
Protein: p.Ser61Pro
Coding: c.181T>C
MANE Select: NM_144672
dbSNP: rs369772866
Type: single nucleotide variant
Location: chr16:21681739 (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

hearing loss disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OTOA p.Ser61Ala Uncertain significance ★★ ⚠ same residue
OTOA p.Arg467Cys Uncertain significance ★★ ⚠ same condition
OTOA p.Leu1126Pro Uncertain significance ★★ ⚠ same condition
OTOA p.Ala765del Uncertain significance ★ same condition
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

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-ser61pro (accessed [today's date]).

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