OTOG p.Ala48=
c.144C>G · rs58448442 · VCV805107
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.02%, afr) — 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 -1.4 | GERP -3.8 |
| Overall | ||
| CADD | 1.941 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.02%
African / African-American · 3,215/53,428 alleles
Filtering AF
5.84%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.77%
Overall
0.611%
3,679/602,012 alleles · common
exomes 1,034/449,808 · genomes 2,645/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.02% | 17 |
| Remaining individualsnot grpmax-eligible | 0.778% | 129 |
| Middle Eastern | 0.56% | 179 |
| Admixed American | 0.533% | 188 |
| European (non-Finnish) | 0.022% | 4,554 |
| South Asian | 0.00344% | 29,044 |
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.Ala48=
- Coding
- c.144C>G
- MANE Select
- NM_001292063
- dbSNP
- rs58448442
- Type
- single nucleotide variant
- Location
- chr11:17547976 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 (gnomAD)
- Residue 48
- the 'disordered' region
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-ala48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown