Is TMC8 p.Val304fs (c.903_910dup) pathogenic?

TMC8 p.Val304fs (c.903910dup) is classified Pathogenic in TMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). Associated with epidermodysplasia verruciformis, susceptibility to, 2.

What condition is associated with TMC8 p.Val304fs (c.903_910dup)?

TMC8 p.Val304fs (c.903_910dup) is associated with epidermodysplasia verruciformis, susceptibility to, 2 (ClinVar).

TMC8 p.Val304fs

c.903_910dup · VCV4293115

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

epidermodysplasia verruciformis, susceptibility to, 2

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 8 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.55	GERP -0.92

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: TMC8
Protein: p.Val304fs
Coding: c.903_910dup
MANE Select: NM_152468
Type: Duplication
Location: chr17:78134477 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.77

Full TMC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermodysplasia verruciformis, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMC8 p.Val304Ile Likely benign ★ same residue
TMC8 c.1824-1G>C Pathogenic/Likely pathogenic ★★ same condition
TMC8 p.Arg295fs Pathogenic ★★ same condition
TMC8 p.Ala598Thr Uncertain significance ★★ ⚠ same condition
TMC8 p.Glu638Ter Uncertain significance ★★ same condition
TMC8 c.1823+15C>A Benign ★★ same condition
TMC8 c.988-4G>T Benign ★★ same condition
TMC8 c.*5T>G Benign/Likely benign ★★ 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-val304fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown