Is EDA p.Arg289Gln (c.866_867delinsAA) pathogenic?

EDA p.Arg289Gln (c.866867delinsAA) is classified Uncertain significance in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-24). No gnomAD frequency available for this variant; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg289Gln (c.866_867delinsAA)?

EDA p.Arg289Gln (c.866_867delinsAA) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg289Gln (c.866_867delinsAA) in the general population?

EDA p.Arg289Gln (c.866_867delinsAA) is no gnomAD frequency available for this variant (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.Arg289Gln

c.866_867delinsAA · rs2020226101 · VCV1025451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 4.8, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic

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.Arg289Gln
Coding: c.866_867delinsAA
MANE Select: NM_001399
dbSNP: rs2020226101
Type: Indel
Location: chrX:70033470 (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.Arg289fs Pathogenic ★ same residue
EDA p.Arg289Gly Uncertain significance ★ ⚠ same residue
EDA p.Arg289= Likely benign ★ same residue
EDA c.585_706+6delinsTCCTCCTGGTCC Pathogenic ★ same condition
EDA p.Ala367fs Pathogenic ★ same condition
EDA p.Gly2fs 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-arg289gln (accessed [today's date]).

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