Is DSG4 p.Phe392fs (c.1168_1172dup) pathogenic?

DSG4 p.Phe392fs (c.11681172dup) is classified Pathogenic in DSG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Ultra-rare (popmax 0.0117%, nfe); Associated with ectodermal dysplasia syndrome.

What condition is associated with DSG4 p.Phe392fs (c.1168_1172dup)?

DSG4 p.Phe392fs (c.1168_1172dup) is associated with ectodermal dysplasia syndrome (ClinVar).

How common is DSG4 p.Phe392fs (c.1168_1172dup) in the general population?

DSG4 p.Phe392fs (c.1168_1172dup) is ultra-rare (popmax 0.0117%, nfe) (gnomAD).

DSG4 p.Phe392fs

c.1168_1172dup · rs771756810 · VCV4087738

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, nfe)

Conditions

ectodermal dysplasia syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.94	GERP -4, phastCons 0.003
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% European (non-Finnish) · 138/1,179,966 alleles

Filtering AF 0.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00948%

Overall 0.0102% 164/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.1%	91
Remaining individualsnot grpmax-eligible	0.0128%	7,811
European (non-Finnish)grpmax	0.0117%	8,550
Admixed American	0.00833%	12,001
African / African-American	0.004%	24,979

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.Phe392fs
Coding: c.1168_1172dup
dbSNP: rs771756810
Type: Duplication
Location: chr18:31399433 (GRCh38)

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

Disease context

ectodermal dysplasia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-phe392fs (accessed [today's date]).

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