Is EDA p.Ala249fs (c.743dup) pathogenic?

EDA p.Ala249fs (c.743dup) is classified Likely pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-19). Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Ala249fs (c.743dup)?

EDA p.Ala249fs (c.743dup) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How is Hypohidrotic ectodermal dysplasia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EDA p.Ala249fs

c.743dup · VCV4855148

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 4.8, phastCons 1

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

Variant & gene context

Gene: EDA
Protein: p.Ala249fs
Coding: c.743dup
MANE Select: NM_001399
Type: Duplication
Location: chrX:70030468 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 249: a β-strand; the thd domain

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.Cys25fs Pathogenic ★★ same condition
EDA p.Gly201fs Pathogenic ★★ same condition
EDA p.Ser110fs Pathogenic/Likely pathogenic ★★ same condition
EDA p.Ser91fs Pathogenic ★★ same condition
EDA c.396+4dup Pathogenic ★ same condition
EDA p.Ala34fs Pathogenic ★ same condition
EDA p.Gln108fs Pathogenic ★ same condition
EDA p.Gln197fs 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-ala249fs (accessed [today's date]).

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