TMC1 p.Asp560=
c.1680C>T · rs773672736 · VCV2996195
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00503%, amr)
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 1.8 | GERP -1.5, phastCons 1 |
| Overall | ||
| CADD | 4.129 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00503%
Admixed American · 3/59,600 alleles
Filtering AF
0.00134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00067%
Overall
0.000186%
3/1,609,308 alleles · very rare
exomes 3/1,460,978 · genomes 0/148,330 · 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
- TMC1
- Protein
- p.Asp560=
- Coding
- c.1680C>T
- MANE Select
- NM_138691
- dbSNP
- rs773672736
- Type
- single nucleotide variant
- Location
- chr9:72805495 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 1 PDB
Similar variants
- TMC1 p.Asp560Val Uncertain significance ★ ⚠ same residue
- TMC1 p.Asp560fs Likely pathogenic ★ 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
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-asp560 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown