Is TMC8 p.Gly93= (c.279G>A) pathogenic?

TMC8 p.Gly93= (c.279G>A) is classified Benign/Likely benign in TMC8 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Low-frequency (popmax 2.09%, afr); Associated with epidermodysplasia verruciformis.

What condition is associated with TMC8 p.Gly93= (c.279G>A)?

TMC8 p.Gly93= (c.279G>A) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC8 p.Gly93= (c.279G>A) in the general population?

TMC8 p.Gly93= (c.279G>A) is low-frequency (popmax 2.09%, afr) (gnomAD).

How is Inherited epidermodysplasia verruciformis inherited?

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

TMC8 p.Gly93=

c.279G>A · rs201749146 · VCV791676

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, afr)

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 -0.52	GERP -1.4, phastCons 0.004
Overall
CADD	8.654	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% African / African-American · 1,521/72,920 alleles

Filtering AF 2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.96%

Overall 0.121% 1,848/1,532,924 alleles · low-frequency exomes 955/1,380,630 · genomes 893/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.09%	48
Remaining individualsnot grpmax-eligible	0.189%	529
Middle Eastern	0.177%	566
Admixed American	0.148%	678
European (non-Finnish)	0.0112%	8,950
Ashkenazi Jewishnot grpmax-eligible	0.00351%	28,502

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.Gly93=
Coding: c.279G>A
MANE Select: NM_152468
dbSNP: rs201749146
Type: single nucleotide variant
Location: chr17:78132011 (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-gly93 (accessed [today's date]).

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