Is EDA p.Ser305fs (c.912_913dup) pathogenic?

EDA p.Ser305fs (c.912913dup) is classified Pathogenic in EDA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2009-03-01). Absent from gnomAD; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Ser305fs (c.912_913dup)?

EDA p.Ser305fs (c.912_913dup) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Ser305fs (c.912_913dup) in the general population?

EDA p.Ser305fs (c.912_913dup) is absent from gnomAD (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.Ser305fs

c.912_913dup · rs1569406514 · VCV11047

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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, 15 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 7.6	GERP 4.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EDA
Protein: p.Ser305fs
Coding: c.912_913dup
MANE Select: NM_001399
dbSNP: rs1569406514
Type: Microsatellite
Location: chrX:70033513 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 305: 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.Ser305Arg Likely pathogenic ★ same residue
EDA p.Ser305Asn Uncertain significance ★ ⚠ same residue
EDA p.Asn163delinsGlyArgAlaArgTrpLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerTer Pathogenic ★ same condition
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

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-ser305fs (accessed [today's date]).

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