Is DSG4 p.Pro916= (c.2748A>G) pathogenic?

DSG4 p.Pro916= (c.2748A>G) is classified Benign in DSG4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 52.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with hypotrichosis 6.

What condition is associated with DSG4 p.Pro916= (c.2748A>G)?

DSG4 p.Pro916= (c.2748A>G) 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.Pro916=

Q: How common is DSG4 p.Pro916= (c.2748A>G) in the general population?

DSG4 p.Pro916= (c.2748A>G) is common (popmax 52.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2748A>G · rs12960081 · VCV326452

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 52.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

hypotrichosis 6

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -5.3	GERP -3.7
Overall
CADD	0.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.5% East Asian · 23,551/44,854 alleles

Filtering AF 51.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.7%

Overall 46.4% 749,476/1,613,818 alleles · common exomes 687,231/1,461,868 · genomes 62,245/151,950 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	66.5%	2
East Asiangrpmax	52.5%	2
European (non-Finnish)	48.2%	2
Admixed American	46.6%	2
Middle Eastern	46.5%	2
Remaining individualsnot grpmax-eligible	46.2%	2
Finnishnot grpmax-eligible	45.1%	2
Ashkenazi Jewishnot grpmax-eligible	45%	2
South Asian	42.3%	2
African / African-American	22.4%	4

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.Pro916=
Coding: c.2748A>G
MANE Select: NM_177986
dbSNP: rs12960081
Type: single nucleotide variant
Location: chr18:31413220 (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-pro916 (accessed [today's date]).

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