Is OTOG p.Arg231fs (c.691_692del) pathogenic?

OTOG p.Arg231fs (c.691692del) is classified Pathogenic in OTOG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-11). Associated with OTOG-related disorder.

What condition is associated with OTOG p.Arg231fs (c.691_692del)?

OTOG p.Arg231fs (c.691_692del) is associated with OTOG-related disorder (ClinVar).

OTOG p.Arg231fs

c.691_692del · VCV4910852

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

OTOG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP -0.58, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: OTOG
Protein: p.Arg231fs
Coding: c.691_692del
MANE Select: NM_001292063
Type: Microsatellite
Location: chr11:17557144 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 (gnomAD)
Residue 231: the vwfd 1 domain

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

Disease context

OTOG-related disorder

Similar variants

OTOG c.2606-16TCT[2] Likely benign same condition
OTOG c.2606-8_2606-4del Likely benign same condition
OTOG c.2561+1del Likely pathogenic ★★ same condition
OTOG c.6934-2A>G Likely pathogenic ★★ same condition
OTOG c.996+1G>T Pathogenic ★★ same condition
OTOG p.Ala2452fs Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Arg1153Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Arg1903Ter Pathogenic/Likely pathogenic ★★ 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/otog-p-arg231fs (accessed [today's date]).

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