Is OTOA p.Arg202Pro (c.605G>C) pathogenic?

OTOA p.Arg202Pro (c.605G>C) is classified Uncertain significance in OTOA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1245); Ultra-rare (popmax 0.0458%, nfe); Associated with Inborn genetic diseases.

What condition is associated with OTOA p.Arg202Pro (c.605G>C)?

OTOA p.Arg202Pro (c.605G>C) is associated with Inborn genetic diseases (ClinVar).

How common is OTOA p.Arg202Pro (c.605G>C) in the general population?

OTOA p.Arg202Pro (c.605G>C) is ultra-rare (popmax 0.0458%, nfe) (gnomAD).

What do computational predictors say about OTOA p.Arg202Pro (c.605G>C)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

OTOA p.Arg202Pro

c.605G>C · rs142850013 · VCV229068

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -2.5
Regional constraint	o/e 0.92	unconstrained · MANE · 52 kb · p 0.02 · regional, not allelic
Overall
CADD	0.005	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0458% European (non-Finnish) · 540/1,179,936 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0413%

Overall 0.0372% 600/1,613,650 alleles · ultra-rare exomes 549/1,461,690 · genomes 51/151,960 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0458%	2,185
Finnishnot grpmax-eligible	0.0407%	2,459
Admixed American	0.0283%	3,528
Remaining individualsnot grpmax-eligible	0.024%	4,165
Middle Eastern	0.0167%	5,982
African / African-American	0.00133%	74,924

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.Arg202Pro
Coding: c.605G>C
MANE Select: NM_144672
dbSNP: rs142850013
Type: single nucleotide variant
Location: chr16:21687618 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OTOA p.Arg202Trp Uncertain significance ★ ⚠ same residue
OTOA p.Arg202Gln Uncertain significance ★ ⚠ same residue
OTOA p.Ala364Thr Uncertain significance ★★ ⚠ same condition
OTOA p.Ala40Val Uncertain significance ★★ ⚠ same condition
OTOA p.Ala477Pro Uncertain significance ★★ ⚠ same condition
OTOA p.Arg1027Trp Uncertain significance ★★ ⚠ same condition
OTOA p.Arg29Lys Uncertain significance ★★ ⚠ same condition
OTOA p.Arg475Lys 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-arg202pro (accessed [today's date]).

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