TMC1 p.Phe504fs
c.1512del · VCV3601891
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
autosomal recessive nonsyndromic hearing loss 7
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 17 of 24 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -4.5 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TMC1
- Protein
- p.Phe504fs
- Coding
- c.1512del
- MANE Select
- NM_138691
- Type
- Deletion
- Location
- chr9:72792293 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.96 · 1 PDB
Similar variants
- TMC1 p.Asn50fs Pathogenic/Likely pathogenic ★★ same condition
- TMC1 p.Met413fs Pathogenic ★★ same condition
- TMC1 c.2125_2129+7del Pathogenic ★ same condition
- TMC1 c.(64+1_65-1 Pathogenic ★ same condition
- TMC1 c.65-4_77del Pathogenic ★ same condition
- TMC1 p.Ala237fs Pathogenic ★ same condition
- TMC1 p.Ala712fs Pathogenic ★ same condition
- TMC1 p.Ala726fs 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/tmc1-p-phe504fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown