Is EDA p.Phe329fs (c.984dup) pathogenic?

EDA p.Phe329fs (c.984dup) is classified Pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Phe329fs (c.984dup)?

EDA p.Phe329fs (c.984dup) 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.Phe329fs

c.984dup · VCV3724125

Pathogenic Single submitter

Classification

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 in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: EDA
Protein: p.Phe329fs
Coding: c.984dup
MANE Select: NM_001399
Type: Duplication
Location: chrX:70035414 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 329: 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.Phe329Ser Pathogenic ★ same residue
EDA p.Phe329Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
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.Ala249fs 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-phe329fs (accessed [today's date]).

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