TMC1 p.Ala232=
c.696C>T · rs112843964 · VCV805671
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.191%, 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 -0.44 | GERP -4.3, phastCons 0.13 |
| Overall | ||
| CADD | 6.253 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.191%
African / African-American · 143/75,018 alleles
Filtering AF
0.165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.155%
Overall
0.0114%
184/1,614,052 alleles · rare
exomes 116/1,461,832 · genomes 68/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.191% | 525 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,976 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.0117% | 8,572 |
| East Asian | 0.00223% | 44,872 |
| South Asian | 0.0022% | 45,538 |
| European (non-Finnish) | 0.000763% | 131,109 |
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.Ala232=
- Coding
- c.696C>T
- MANE Select
- NM_138691
- dbSNP
- rs112843964
- Type
- single nucleotide variant
- Location
- chr9:72754839 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 1 PDB
Similar variants
- TMC1 p.Ala232Val 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-ala232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown