Is EDA p.Pro188fs (c.560dup) pathogenic?

EDA p.Pro188fs (c.560dup) is classified Pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-25). Absent from gnomAD; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Pro188fs (c.560dup)?

EDA p.Pro188fs (c.560dup) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Pro188fs (c.560dup) in the general population?

EDA p.Pro188fs (c.560dup) is absent from gnomAD (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

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

EDA p.Pro188fs

c.560dup · rs1556098384 · VCV458658

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 3.9, phastCons 1
Region caveats
Repeat context	tandem	AGGACCTCCAGGACCCA simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EDA
Protein: p.Pro188fs
Coding: c.560dup
MANE Select: NM_001399
dbSNP: rs1556098384
Type: Duplication
Location: chrX:70027887 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 188: a UniProt-annotated variant site (in xhed); the collagen-like domain; the 'disordered' region

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

Disease context

X-linked hypohidrotic ectodermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypohidrotic ectodermal dysplasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

EDA p.Pro188Ser Uncertain significance ★ ⚠ same residue
EDA p.Pro188= Likely benign ★ same residue
EDA p.Cys25fs Pathogenic ★★ same condition
EDA p.Gly201fs Pathogenic ★★ same condition
EDA p.Ser110fs Pathogenic/Likely pathogenic ★★ same condition
EDA p.Ser91fs Pathogenic ★★ same condition
EDA c.396+4dup Pathogenic ★ same condition
EDA p.Ala249fs Likely pathogenic ★ 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/eda-p-pro188fs (accessed [today's date]).

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