Is DSG4 p.Ser285= (c.855G>A) pathogenic?

DSG4 p.Ser285= (c.855G>A) is classified Benign/Likely benign in DSG4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-10). Low-frequency (popmax 4.55%, afr); Associated with hypotrichosis 6.

What condition is associated with DSG4 p.Ser285= (c.855G>A)?

DSG4 p.Ser285= (c.855G>A) is associated with hypotrichosis 6 (ClinVar).

How common is DSG4 p.Ser285= (c.855G>A) in the general population?

DSG4 p.Ser285= (c.855G>A) is low-frequency (popmax 4.55%, 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.Ser285=

c.855G>A · rs35210710 · VCV326426

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.55%, 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 -5.4	GERP -4
Overall
CADD	2.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.55% African / African-American · 3,412/74,976 alleles

Filtering AF 4.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.37%

Overall 0.233% 3,752/1,613,584 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.55%	22
Remaining individualsnot grpmax-eligible	0.243%	411
Middle Eastern	0.215%	466
Admixed American	0.195%	513
European (non-Finnish)	0.00466%	21,450
East Asian	0.00223%	44,758
South Asian	0.0022%	45,527

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.Ser285=
Coding: c.855G>A
dbSNP: rs35210710
Type: single nucleotide variant
Location: chr18:31392190 (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-ser285 (accessed [today's date]).

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