Is TMC8 p.Ala85= (c.255C>T) pathogenic?

TMC8 p.Ala85= (c.255C>T) is classified Likely benign in TMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-30). Very rare (popmax 8.75e-05%, nfe); Associated with epidermodysplasia verruciformis.

What condition is associated with TMC8 p.Ala85= (c.255C>T)?

TMC8 p.Ala85= (c.255C>T) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC8 p.Ala85= (c.255C>T) in the general population?

TMC8 p.Ala85= (c.255C>T) is very rare (popmax 8.75e-05%, nfe) (gnomAD).

How is Inherited epidermodysplasia verruciformis inherited?

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

TMC8 p.Ala85=

c.255C>T · rs2145577870 · VCV1113281

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.75e-05%, nfe)

Conditions

epidermodysplasia verruciformis

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.68	GERP 0.093
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.75e-05% European (non-Finnish) · 1/1,143,156 alleles

Overall 6.55e-05% 1/1,527,240 alleles · very rare exomes 1/1,374,898 · genomes 0/152,342 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TMC8
Protein: p.Ala85=
Coding: c.255C>T
MANE Select: NM_152468
dbSNP: rs2145577870
Type: single nucleotide variant
Location: chr17:78131987 (GRCh38)

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

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-ala85 (accessed [today's date]).

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