TMC8 p.Leu476=
c.1428G>A · rs2145710163 · VCV1656470
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
epidermodysplasia verruciformis
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 2.4 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 9.501 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TMC8
- Protein
- p.Leu476=
- Coding
- c.1428G>A
- MANE Select
- NM_152468
- dbSNP
- rs2145710163
- Type
- single nucleotide variant
- Location
- chr17:78138083 (GRCh38)
- Gene constraint
- LOEUF 1.201 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 76.77
- Residue 476
- the 'tmc domain' region; a UniProt-annotated variant site (in ev2)
Disease context
epidermodysplasia verruciformis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Inherited epidermodysplasia verruciformis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
Similar variants
- TMC8 c.1824-1G>C Pathogenic/Likely pathogenic ★★ same condition
- TMC8 c.449-1G>T Likely pathogenic ★★ same condition
- TMC8 p.Arg190Ter Pathogenic ★★ same condition
- TMC8 p.Ala188Val Uncertain significance ★★ ⚠ same condition
- TMC8 p.Ala290Thr Uncertain significance ★★ ⚠ same condition
- TMC8 p.Ala313Val Uncertain significance ★★ ⚠ same condition
- TMC8 p.Ala316Thr Uncertain significance ★★ ⚠ same condition
- TMC8 p.Ala345Thr Uncertain significance ★★ ⚠ 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/tmc8-p-leu476 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown