Is OTOG p.Val2003fs (c.6007del) pathogenic?

OTOG p.Val2003fs (c.6007del) is classified Likely pathogenic in OTOG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). Very rare (popmax 0.000523%, nfe); Associated with OTOG-related disorder.

What condition is associated with OTOG p.Val2003fs (c.6007del)?

OTOG p.Val2003fs (c.6007del) is associated with OTOG-related disorder (ClinVar).

How common is OTOG p.Val2003fs (c.6007del) in the general population?

OTOG p.Val2003fs (c.6007del) is very rare (popmax 0.000523%, nfe) (gnomAD).

OTOG p.Val2003fs

c.6007del · VCV4910921

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000523%, nfe)

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 36 of 56
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.91	GERP -3.9
Overall
CADD	0.355	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000523% European (non-Finnish) · 6/1,147,006 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000387% 6/1,550,470 alleles · very rare

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: OTOG
Protein: p.Val2003fs
Coding: c.6007del
MANE Select: NM_001292063
Type: Deletion
Location: chr11:17611306 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 (gnomAD)

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

Disease context

OTOG-related disorder

Similar variants

OTOG c.2561+1del Likely pathogenic ★★ same condition
OTOG p.Asp2241fs Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Lys411fs Likely pathogenic ★ same condition
OTOG p.Met1581fs Likely pathogenic ★ same condition
OTOG p.Thr975fs 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

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-val2003fs (accessed [today's date]).

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