Is DSG4 p.Ile513= (c.1539C>T) pathogenic?

DSG4 p.Ile513= (c.1539C>T) is classified Benign/Likely benign in DSG4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). Low-frequency (popmax 4.21%, afr); Associated with hypotrichosis 6.

What condition is associated with DSG4 p.Ile513= (c.1539C>T)?

DSG4 p.Ile513= (c.1539C>T) is associated with hypotrichosis 6 (ClinVar).

How common is DSG4 p.Ile513= (c.1539C>T) in the general population?

DSG4 p.Ile513= (c.1539C>T) is low-frequency (popmax 4.21%, afr) (gnomAD).

How is Hypotrichosis simplex inherited?

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

DSG4 p.Ile513=

c.1539C>T · rs9945567 · VCV710517

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.21%, afr)

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 0.49	GERP 1.1, phastCons 0.99
Overall
CADD	1.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.21% African / African-American · 3,161/75,026 alleles

Filtering AF 4.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.04%

Overall 0.221% 3,575/1,614,042 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.21%	24
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.282%	355
Admixed American	0.257%	390
European (non-Finnish)	0.00551%	18,153
South Asian	0.0011%	91,072

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.Ile513=
Coding: c.1539C>T
dbSNP: rs9945567
Type: single nucleotide variant
Location: chr18:31403537 (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-ile513 (accessed [today's date]).

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