TBC1D24 p.Pro282=
c.846T>C · rs1174059685 · VCV2942989
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
2
autosomal dominant nonsyndromic hearing loss 65
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 -12 | GERP -2.5 |
| Overall | ||
| CADD | 0.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,036 alleles
Overall
6.2e-05%
1/1,613,950 alleles · very rare
exomes 1/1,461,596 · genomes 0/152,354 · joint denominator
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
- TBC1D24
- Protein
- p.Pro282=
- Coding
- c.846T>C
- MANE Select
- NM_001199107
- dbSNP
- rs1174059685
- Type
- single nucleotide variant
- Location
- chr16:2496994 (GRCh38)
- Gene constraint
- LOEUF 1.214 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.46
Similar variants
- TBC1D24 p.Pro282Arg Pathogenic/Likely pathogenic ★★ same residue
- TBC1D24 p.Pro282Ser Uncertain significance ★ ⚠ same residue
- TBC1D24 c.1302+1G>T Likely pathogenic ★★ same condition
- TBC1D24 c.965+2T>C Pathogenic/Likely pathogenic ★★ same condition
- TBC1D24 c.983+1G>C Likely pathogenic ★★ same condition
- TBC1D24 p.Ala289Val Likely pathogenic ★★ same condition
- TBC1D24 p.Ala39Val Pathogenic ★★ ⚠ same condition
- TBC1D24 p.Ala500Val 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/tbc1d24-p-pro282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown