Is TMC8 p.Pro160= (c.480G>A) pathogenic?

TMC8 p.Pro160= (c.480G>A) is classified Benign/Likely benign in TMC8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). Rare (popmax 0.33%, eas); Associated with epidermodysplasia verruciformis.

What condition is associated with TMC8 p.Pro160= (c.480G>A)?

TMC8 p.Pro160= (c.480G>A) is associated with epidermodysplasia verruciformis (ClinVar).

How common is TMC8 p.Pro160= (c.480G>A) in the general population?

TMC8 p.Pro160= (c.480G>A) is rare (popmax 0.33%, eas) (gnomAD).

How is Inherited epidermodysplasia verruciformis inherited?

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

TMC8 p.Pro160=

c.480G>A · rs150261314 · VCV721459

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.33%, eas)

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>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -0.91, phastCons 0.3
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.33% East Asian · 148/44,886 alleles

Filtering AF 0.286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0211% 341/1,614,208 alleles · rare exomes 317/1,461,866 · genomes 24/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.33%	303
European (non-Finnish)	0.0149%	6,705
Remaining individualsnot grpmax-eligible	0.0144%	6,946
African / African-American	0.00799%	12,510
Admixed American	0.00333%	30,015

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.Pro160=
Coding: c.480G>A
MANE Select: NM_152468
dbSNP: rs150261314
Type: single nucleotide variant
Location: chr17:78132819 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.77

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

Similar variants

TMC8 p.Pro160Leu Uncertain significance ★ ⚠ same residue
TMC8 c.1824-1G>C Pathogenic/Likely pathogenic ★★ same condition
TMC8 c.449-1G>T Likely pathogenic ★★ same condition
TMC8 p.Arg190Ter Pathogenic ★★ same condition
TMC8 p.Ala188Val Uncertain significance ★★ ⚠ same condition
TMC8 p.Ala290Thr Uncertain significance ★★ ⚠ same condition
TMC8 p.Ala313Val Uncertain significance ★★ ⚠ same condition
TMC8 p.Ala316Thr 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/tmc8-p-pro160 (accessed [today's date]).

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