Is TMC6 p.Pro286fs (c.846_855dup) pathogenic?

TMC6 p.Pro286fs (c.846855dup) is classified Pathogenic in TMC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). No gnomAD frequency available for this variant; Associated with epidermodysplasia verruciformis.

What condition is associated with TMC6 p.Pro286fs (c.846_855dup)?

TMC6 p.Pro286fs (c.846_855dup) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC6 p.Pro286fs (c.846_855dup) in the general population?

TMC6 p.Pro286fs (c.846_855dup) 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.

TMC6 p.Pro286fs

c.846_855dup · rs1468619952 · VCV2694155

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP -2.5, phastCons 1

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

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: TMC6
Protein: p.Pro286fs
Coding: c.846_855dup
MANE Select: NM_001127198
dbSNP: rs1468619952
Type: Duplication
Location: chr17:78124559 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.56

Full TMC6 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

TMC6 p.Pro286= Benign/Likely benign ★★ same residue
TMC6 p.Leu475fs Pathogenic ★ same condition
TMC6 p.Thr444fs Pathogenic ★ same condition
TMC6 p.Val383fs Pathogenic ★ same condition
TMC6 p.Pro659_Phe661dup Uncertain significance ★ same condition
TMC6 c.1383+10dup Likely benign ★ same condition
TMC6 c.272-19_272-15dup Likely benign ★ same condition
TMC6 c.57-17dup 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/tmc6-p-pro286fs (accessed [today's date]).

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