Is TMC8 p.Leu95= (c.285C>G) pathogenic?

TMC8 p.Leu95= (c.285C>G) is classified Likely benign in TMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Very rare (popmax 0.000436%, nfe); Associated with epidermodysplasia verruciformis.

What condition is associated with TMC8 p.Leu95= (c.285C>G)?

TMC8 p.Leu95= (c.285C>G) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC8 p.Leu95= (c.285C>G) in the general population?

TMC8 p.Leu95= (c.285C>G) is very rare (popmax 0.000436%, nfe) (gnomAD).

How is Inherited epidermodysplasia verruciformis inherited?

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

TMC8 p.Leu95=

c.285C>G · rs2075001081 · VCV2834241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000436%, 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 0.31	GERP -2.4, phastCons 0.93
Overall
CADD	7.947	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000436% European (non-Finnish) · 5/1,145,866 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000326% 5/1,533,596 alleles · very rare exomes 5/1,381,304 · genomes 0/152,292 · 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.Leu95=
Coding: c.285C>G
MANE Select: NM_152468
dbSNP: rs2075001081
Type: single nucleotide variant
Location: chr17:78132017 (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-leu95 (accessed [today's date]).

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