OTOG p.Pro1228=
c.3684G>A · rs755990926 · VCV2672462
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00506%, nfe)
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 -13 | GERP -4.4 |
| Overall | ||
| CADD | 0.003 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00506%
European (non-Finnish) · 58/1,147,014 alleles
Filtering AF
0.00397%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00363%
Overall
0.00406%
63/1,550,572 alleles · very rare
exomes 59/1,398,384 · genomes 4/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00506% | 19,776 |
| Remaining individualsnot grpmax-eligible | 0.00499% | 20,038 |
| African / African-American | 0.00137% | 73,034 |
| South Asian | 0.00119% | 84,058 |
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.Pro1228=
- Coding
- c.3684G>A
- MANE Select
- NM_001292063
- dbSNP
- rs755990926
- Type
- single nucleotide variant
- Location
- chr11:17599672 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 (gnomAD)
Similar variants
- OTOG p.Pro1228Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- OTOG p.Pro1228Thr 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-pro1228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown