Is TMC8 p.Val484Phe (c.1449_1450delinsCT) pathogenic?

TMC8 p.Val484Phe (c.14491450delinsCT) is classified Uncertain significance in TMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-08). No gnomAD frequency available for this variant; Associated with epidermodysplasia verruciformis.

What condition is associated with TMC8 p.Val484Phe (c.1449_1450delinsCT)?

TMC8 p.Val484Phe (c.1449_1450delinsCT) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC8 p.Val484Phe (c.1449_1450delinsCT) in the general population?

TMC8 p.Val484Phe (c.1449_1450delinsCT) is no gnomAD frequency available for this variant (gnomAD).

How is Inherited epidermodysplasia verruciformis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TMC8 p.Val484Phe

c.1449_1450delinsCT · rs2145710563 · VCV1461519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

epidermodysplasia verruciformis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -10	GERP -3.4
Regional constraint	o/e 0.97	unconstrained · MANE · 9,520 bp · p 0.44 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TMC8
Protein: p.Val484Phe
Coding: c.1449_1450delinsCT
MANE Select: NM_152468
dbSNP: rs2145710563
Type: Indel
Location: chr17:78138104 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.77
Residue 484: the 'tmc domain' region; a UniProt-annotated variant site (in ev2)

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

Disease context

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

For Inherited epidermodysplasia verruciformis (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

TMC8 c.668+5_668+6delinsAC Uncertain significance ★ same condition
TMC8 p.Glu468Leu Uncertain significance ★ same condition
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.Arg295fs Pathogenic ★★ same condition
TMC8 p.Ala188Val Uncertain significance ★★ ⚠ same condition
TMC8 p.Ala290Thr 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-val484phe (accessed [today's date]).

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