Is TMC6 p.Arg94= (c.280C>A) pathogenic?

TMC6 p.Arg94= (c.280C>A) is classified Likely benign in TMC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-25). No allele count reported in gnomAD v4.1 (AN 1,550,804); Associated with epidermodysplasia verruciformis.

What condition is associated with TMC6 p.Arg94= (c.280C>A)?

TMC6 p.Arg94= (c.280C>A) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC6 p.Arg94= (c.280C>A) in the general population?

TMC6 p.Arg94= (c.280C>A) is no allele count reported in gnomAD v4.1 (AN 1,550,804) (gnomAD).

How is Inherited epidermodysplasia verruciformis inherited?

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

TMC6 p.Arg94=

c.280C>A · rs121908327 · VCV1095753

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,550,804)

Conditions

epidermodysplasia verruciformis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP -0.069, phastCons 1
Overall
CADD	13.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,550,804). 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: TMC6
Protein: p.Arg94=
Coding: c.280C>A
MANE Select: NM_001127198
dbSNP: rs121908327
Type: single nucleotide variant
Location: chr17:78125876 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.56
Residue 94: a modified residue (omega-n-methylarginine)

Full TMC6 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

Similar variants

TMC6 p.Arg94Ter Pathogenic ★★ same residue
TMC6 p.Arg94Gln Uncertain significance ★ ⚠ same residue
TMC8 p.Ala94Ser Uncertain significance ★ ⚠ same residue
TMC6 c.1383+4C>T Uncertain significance ★★ same condition
TMC6 p.Ala124Pro Uncertain significance ★★ ⚠ same condition
TMC6 p.Ala212Val Uncertain significance ★★ ⚠ same condition
TMC6 p.Ala233Thr Uncertain significance ★★ ⚠ same condition
TMC6 p.Ala380Thr Uncertain significance ★★ ⚠ 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/tmc6-p-arg94 (accessed [today's date]).

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