TMC1 p.Asp307=
c.921T>C · rs1216176717 · VCV743361
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, afr)
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 0.17 | GERP -4.5, phastCons 0.99 |
| Overall | ||
| CADD | 5.411 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
African / African-American · 5/74,902 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00162%
Overall
0.000372%
6/1,613,934 alleles · very rare
exomes 3/1,461,786 · genomes 3/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00668% | 14,980 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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
- TMC1
- Protein
- p.Asp307=
- Coding
- c.921T>C
- MANE Select
- NM_138691
- dbSNP
- rs1216176717
- Type
- single nucleotide variant
- Location
- chr9:72788375 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 1 PDB
Similar variants
- TMC1 p.Asp307Gly Uncertain significance ★ ⚠ same residue
- TMC1 c.1405-2A>T Likely pathogenic ★★ same type
- TMC1 c.1763+3A>G Pathogenic/Likely pathogenic ★★ same type
- TMC1 c.236+1G>A Pathogenic ★★ same type
- TMC1 c.236+1G>T Pathogenic ★★ same type
- TMC1 c.64+2T>A Pathogenic/Likely pathogenic ★★ same type
- TMC1 c.741+1G>A Pathogenic/Likely pathogenic ★★ same type
- TMC1 c.884+1G>A 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/tmc1-p-asp307 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown