OTOG p.Val353=
c.1059C>T · rs74921579 · VCV226859
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.21%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.34 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 13.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.21%
African / African-American · 885/73,188 alleles
Filtering AF
1.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.12%
Overall
0.071%
1,101/1,550,458 alleles · low-frequency
exomes 567/1,398,092 · genomes 534/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.21% | 83 |
| Middle Eastern | 0.234% | 428 |
| Remaining individualsnot grpmax-eligible | 0.131% | 761 |
| Admixed American | 0.127% | 785 |
| European (non-Finnish) | 0.0048% | 20,855 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00349% | 28,650 |
| South Asian | 0.00238% | 42,032 |
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.Val353=
- Coding
- c.1059C>T
- MANE Select
- NM_001292063
- dbSNP
- rs74921579
- Type
- single nucleotide variant
- Location
- chr11:17558600 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 (gnomAD)
Similar variants
- 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
- OTOG p.Arg2175Ter Pathogenic/Likely pathogenic ★★ same type
- OTOG p.Arg2473Ter 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-val353 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown