Is EDA p.Pro191fs (c.572del) pathogenic?

EDA p.Pro191fs (c.572del) is classified Pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Absent from gnomAD v4.1; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Pro191fs (c.572del)?

EDA p.Pro191fs (c.572del) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Pro191fs (c.572del) in the general population?

EDA p.Pro191fs (c.572del) is absent from gnomAD v4.1 (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.Pro191fs

c.572del · rs2147509613 · VCV2822020

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,105,681)

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 0.37	GERP -1.1, phastCons 0.75
Region caveats
Repeat context	tandem	(CCAGGACCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,105,681). 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.Pro191fs
Coding: c.572del
MANE Select: NM_001399
dbSNP: rs2147509613
Type: Deletion
Location: chrX:70027898 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 191: 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.202_204IPG[1] Pathogenic/Likely pathogenic ★★ same condition
EDA p.217_219PGP[1] Pathogenic ★★ same condition
EDA p.Ala166fs Pathogenic ★★ same condition
EDA p.Asn185_Pro196del Pathogenic ★★ same condition
EDA p.Gly85fs Pathogenic ★★ same condition
EDA p.Phe317fs Pathogenic ★★ same condition
EDA p.Pro199fs Pathogenic ★★ same condition
EDA p.Pro219_Gly230del Pathogenic/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-pro191fs (accessed [today's date]).

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