Is TMC8 p.Arg295fs (c.883_889del) pathogenic?

TMC8 p.Arg295fs (c.883889del) is classified Pathogenic in TMC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-22). No gnomAD frequency available for this variant; Associated with epidermodysplasia verruciformis, susceptibility to, 2.

How common is TMC8 p.Arg295fs (c.883_889del) in the general population?

TMC8 p.Arg295fs (c.883_889del) is no gnomAD frequency available for this variant (gnomAD).

TMC8 p.Arg295fs

Q: What condition is associated with TMC8 p.Arg295fs (c.883_889del)?

TMC8 p.Arg295fs (c.883_889del) is associated with epidermodysplasia verruciformis, susceptibility to, 2, epidermodysplasia verruciformis (ClinVar).

c.883_889del · rs2510788991 · VCV2444390

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 0.097	GERP -2.5, phastCons 0.62

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: TMC8
Protein: p.Arg295fs
Coding: c.883_889del
MANE Select: NM_152468
dbSNP: rs2510788991
Type: Deletion
Location: chr17:78134454 (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

Also linked: epidermodysplasia verruciformis

Similar variants

TMC8 p.Arg295Cys Uncertain significance ★ ⚠ same residue
TMC8 p.Arg295Gly Uncertain significance ★ ⚠ same residue
TMC8 p.Arg295His Conflicting classifications of pathogenicity ★ ⚠ same residue
TMC8 p.Ala188fs Pathogenic ★ same condition
TMC8 p.Asp142fs Pathogenic ★ same condition
TMC8 p.Asp251fs Pathogenic ★ same condition
TMC8 p.Gln236fs Pathogenic ★ same condition
TMC8 p.Gln291fs 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/tmc8-p-arg295fs (accessed [today's date]).

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