Is EDA p.Arg289= (c.867C>A) pathogenic?

EDA p.Arg289= (c.867C>A) is classified Likely benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-23). Very rare (popmax 9.11e-05%); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg289= (c.867C>A)?

EDA p.Arg289= (c.867C>A) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg289= (c.867C>A) in the general population?

EDA p.Arg289= (c.867C>A) is very rare (popmax 9.11e-05%) (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.Arg289=

c.867C>A · rs1471642587 · VCV1131984

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 3.7, phastCons 1
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.11e-05%

Overall 9.11e-05% 1/1,098,079 alleles · very rare

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: EDA
Protein: p.Arg289=
Coding: c.867C>A
MANE Select: NM_001399
dbSNP: rs1471642587
Type: single nucleotide variant
Location: chrX:70033471 (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.Arg289Gly Uncertain significance ★ ⚠ same residue
EDA p.Arg289fs Pathogenic ★ same residue
EDA p.Arg289Gln Uncertain significance ★ same residue
EDA c.526+5G>T Likely pathogenic ★★ same condition
EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same condition
EDA c.706+1G>A 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-arg289 (accessed [today's date]).

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