Is DSG4 p.Pro1009= (c.3027A>G) pathogenic?

DSG4 p.Pro1009= (c.3027A>G) is classified Uncertain significance in DSG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with hypotrichosis 6.

What condition is associated with DSG4 p.Pro1009= (c.3027A>G)?

DSG4 p.Pro1009= (c.3027A>G) is associated with hypotrichosis 6 (ClinVar).

How common is DSG4 p.Pro1009= (c.3027A>G) in the general population?

DSG4 p.Pro1009= (c.3027A>G) is absent from gnomAD v4.1 (gnomAD).

How is Hypotrichosis simplex inherited?

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

DSG4 p.Pro1009=

c.3027A>G · rs1369959288 · VCV891858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypotrichosis 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -0.77, phastCons 0.98
Overall
CADD	1.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSG4
Protein: p.Pro1009=
Coding: c.3027A>G
MANE Select: NM_177986
dbSNP: rs1369959288
Type: single nucleotide variant
Location: chr18:31413499 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.63
Residue 1009: a UniProt-annotated variant site (in hypt6; significant decrease in interaction with jup and localization to desmosomes)

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

Similar variants

DSG4 p.His386Gln Uncertain significance ★★ ⚠ same condition
DSG4 p.His902Arg Uncertain significance ★★ ⚠ same condition
DSG4 p.Tyr585His Uncertain significance ★★ ⚠ same condition
DSG4 c.*126G>A Benign/Likely benign ★★ same condition
DSG4 c.*31C>T Benign ★★ same condition
DSG4 p.Ala154Thr Benign/Likely benign ★★ ⚠ same condition
DSG4 p.Ile439Thr Benign/Likely benign ★★ ⚠ same condition
DSG4 p.Met1023Ile Benign/Likely benign ★★ 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/dsg4-p-pro1009 (accessed [today's date]).

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