Is DSG4 p.Cys10= (c.30C>T) pathogenic?

DSG4 p.Cys10= (c.30C>T) is classified Benign in DSG4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Common (popmax 20.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with hypotrichosis 6.

What condition is associated with DSG4 p.Cys10= (c.30C>T)?

DSG4 p.Cys10= (c.30C>T) is associated with hypotrichosis 6 (ClinVar).

How is Hypotrichosis simplex inherited?

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

DSG4 p.Cys10=

Q: How common is DSG4 p.Cys10= (c.30C>T) in the general population?

DSG4 p.Cys10= (c.30C>T) is common (popmax 20.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.30C>T · rs36101975 · VCV326416

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 20.7%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

hypotrichosis 6

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 -1.4	GERP -3
Overall
CADD	4.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.7% Middle Eastern · 1,252/6,056 alleles

Filtering AF 19.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.3%

Overall 14.2% 228,338/1,612,720 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	27.4%	4
Middle Easterngrpmax	20.7%	5
Ashkenazi Jewishnot grpmax-eligible	18.4%	5
South Asian	16.1%	6
European (non-Finnish)	14.4%	7
Remaining individualsnot grpmax-eligible	13.8%	7
Finnishnot grpmax-eligible	13.5%	7
African / African-American	13.5%	7
East Asian	11.9%	8
Admixed American	7.97%	13

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DSG4
Protein: p.Cys10=
Coding: c.30C>T
dbSNP: rs36101975
Type: single nucleotide variant
Location: chr18:31376941 (GRCh38)

Full DSG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypotrichosis 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypotrichosis simplex (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

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/dsg4-p-cys10 (accessed [today's date]).

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