OTOG p.Arg758=
c.2274C>T · rs16934404 · VCV226867
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 8.78%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.7 | GERP -4.4 |
| Overall | ||
| CADD | 0.677 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.78%
East Asian · 3,573/40,702 alleles
Filtering AF
8.54%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.44%
Overall
0.74%
11,311/1,528,074 alleles · common
exomes 8,009/1,375,778 · genomes 3,302/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 8.78% | 11 |
| African / African-American | 5.55% | 18 |
| Admixed American | 2.74% | 36 |
| South Asian | 1.39% | 72 |
| Remaining individualsnot grpmax-eligible | 0.944% | 106 |
| Middle Eastern | 0.414% | 241 |
| European (non-Finnish) | 0.0482% | 2,075 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00705% | 14,188 |
| Finnishnot grpmax-eligible | 0.00673% | 14,849 |
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.Arg758=
- Coding
- c.2274C>T
- MANE Select
- NM_001292063
- dbSNP
- rs16934404
- Type
- single nucleotide variant
- Location
- chr11:17573271 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 (gnomAD)
Similar variants
- OTOG p.Arg758Cys Uncertain significance ★ ⚠ same residue
- OTOG p.Arg758His Uncertain significance ★ same residue
- OTOG c.6934-2A>G Likely pathogenic ★★ same type
- OTOG c.996+1G>T Pathogenic ★★ same type
- OTOG p.Arg1063Ter Pathogenic/Likely pathogenic ★★ same type
- OTOG p.Arg1153Ter Pathogenic/Likely pathogenic ★★ same type
- OTOG p.Arg1222Ter Pathogenic/Likely pathogenic ★★ same type
- OTOG p.Arg1903Ter 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/otog-p-arg758 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown