Is EDA p.Leu296fs (c.886_899delinsG) pathogenic?

EDA p.Leu296fs (c.886899delinsG) is classified Likely pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Leu296fs (c.886_899delinsG)?

EDA p.Leu296fs (c.886_899delinsG) 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.Leu296fs

c.886_899delinsG · VCV4814926

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (7 of 8, 38 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 4.8, phastCons 1

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

Variant & gene context

Gene: EDA
Protein: p.Leu296fs
Coding: c.886_899delinsG
MANE Select: NM_001399
Type: Indel
Location: chrX:70033490 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 296: 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 p.Leu296_Val297del Uncertain significance ★ same residue
EDA p.Leu296= 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
EDA p.Leu78fs Pathogenic ★ same condition
EDA p.Lys174fs Pathogenic ★ same condition
EDA p.Arg156Ser Uncertain significance ★ 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-leu296fs (accessed [today's date]).

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