Is EDA p.Asp298= (c.894C>T) pathogenic?

EDA p.Asp298= (c.894C>T) is classified Likely benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). Very rare (popmax 0.00176%, sas); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Asp298= (c.894C>T)?

EDA p.Asp298= (c.894C>T) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Asp298= (c.894C>T) in the general population?

EDA p.Asp298= (c.894C>T) is very rare (popmax 0.00176%, sas) (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.Asp298=

c.894C>T · rs1602623024 · VCV792240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 3.8, phastCons 1
Overall
CADD	13.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% South Asian · 1/56,953 alleles

Overall 0.000165% 2/1,211,339 alleles · very rare exomes 2/1,098,072 · genomes 0/113,267 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00176%	56,953
European (non-Finnish)	0.000112%	895,375

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.Asp298=
Coding: c.894C>T
MANE Select: NM_001399
dbSNP: rs1602623024
Type: single nucleotide variant
Location: chrX:70033498 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 298: the thd domain; a UniProt-annotated variant site (in xhed)

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 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
EDA c.707-13T>G Pathogenic ★★ same condition
EDA c.742-2A>G Pathogenic/Likely pathogenic ★★ same condition
EDA c.924+1G>T Likely pathogenic ★★ same condition
EDA p.Ala349Ser Likely pathogenic ★★ ⚠ same condition
EDA p.Ala349Thr 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-asp298 (accessed [today's date]).

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