OTOG p.Pro2574=
c.7722C>T · rs1260956852 · VCV1185112
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00588%, amr)
Conditions
1
autosomal recessive nonsyndromic hearing loss 18B
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.2 |
| Overall | ||
| CADD | 0.213 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00588%
Admixed American · 3/50,982 alleles
Filtering AF
0.00156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000833%
Overall
0.00148%
23/1,550,410 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00588% | 16,994 |
| African / African-American | 0.00274% | 36,517 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,082 |
| European (non-Finnish) | 0.00148% | 67,468 |
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.Pro2574=
- Coding
- c.7722C>T
- MANE Select
- NM_001292063
- dbSNP
- rs1260956852
- Type
- single nucleotide variant
- Location
- chr11:17635638 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 (gnomAD)
Similar variants
- OTOG p.Arg1063Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Arg1153Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Arg1222Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Arg2175Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Arg2473Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Gln127Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Gln556Ter Pathogenic/Likely pathogenic ★★ same condition
- OTOG p.Gln822Ter 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-pro2574 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown