Is TMC8 p.Glu369= (c.1107G>A) pathogenic?

TMC8 p.Glu369= (c.1107G>A) is classified Benign in TMC8 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 70.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with epidermodysplasia verruciformis.

What condition is associated with TMC8 p.Glu369= (c.1107G>A)?

TMC8 p.Glu369= (c.1107G>A) is associated with epidermodysplasia verruciformis, epidermodysplasia verruciformis, susceptibility to, 2 (ClinVar).

How is Inherited epidermodysplasia verruciformis inherited?

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

TMC8 p.Glu369=

Q: How common is TMC8 p.Glu369= (c.1107G>A) in the general population?

TMC8 p.Glu369= (c.1107G>A) is common (popmax 70.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1107G>A · rs12452890 · VCV403547

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 70.2%, afr) — too common for a highly-penetrant pathogenic allele

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 3.6	GERP 0.42, phastCons 1
Overall
CADD	4.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.2% African / African-American · 52,630/74,952 alleles

Filtering AF 69.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.5%

Overall 51.8% 836,697/1,613,796 alleles · common exomes 748,837/1,461,742 · genomes 87,860/152,054 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	70.2%	1
Middle Eastern	62.7%	2
Admixed American	61.2%	2
Ashkenazi Jewishnot grpmax-eligible	61.2%	2
Finnishnot grpmax-eligible	56.4%	2
Amishnot grpmax-eligible	55.2%	2
Remaining individualsnot grpmax-eligible	52.9%	2
European (non-Finnish)	50.6%	2
South Asian	43.7%	2
East Asian	43.1%	2

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.Glu369=
Coding: c.1107G>A
MANE Select: NM_152468
dbSNP: rs12452890
Type: single nucleotide variant
Location: chr17:78134989 (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

Also linked: epidermodysplasia verruciformis, susceptibility to, 2

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-glu369 (accessed [today's date]).

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