Is EDA p.Arg289fs (c.865del) pathogenic?

EDA p.Arg289fs (c.865del) is classified Pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-02). Absent from gnomAD; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg289fs (c.865del)?

EDA p.Arg289fs (c.865del) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg289fs (c.865del) in the general population?

EDA p.Arg289fs (c.865del) 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.Arg289fs

c.865del · rs2520343256 · VCV1803966

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 7 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 0.5, phastCons 1

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.Arg289fs
Coding: c.865del
MANE Select: NM_001399
dbSNP: rs2520343256
Type: Deletion
Location: chrX:70033466 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 289: a turn; the thd domain; a UniProt-annotated variant site (in sthagx1; decreased interaction with edar for isoform 1; decreased interaction with eda2r for isoform 3; changed downstream signaling); a UniProt-annotated variant site (in sthagx1); a UniProt-annotated variant site (in xhed; when associated in cis with c-290; loss of function in edar-mediated signaling when associated in cis with c-290; not secreted when associated in cis with c-290)

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.Arg289Cys Pathogenic ★★ ⚠ same residue
EDA p.Arg289His Pathogenic/Likely pathogenic ★★ ⚠ same residue
EDA p.Arg289Gln Uncertain significance ★ same residue
EDA p.Arg289Gly Uncertain significance ★ ⚠ same residue
EDA p.Arg289= Likely benign ★ same residue
EDA p.202_204IPG[1] Pathogenic/Likely pathogenic ★★ same condition
EDA p.217_219PGP[1] Pathogenic ★★ same condition
EDA p.Ala166fs 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-arg289fs (accessed [today's date]).

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