Is EDAR c.442+5del pathogenic?

EDAR c.442+5del is classified Uncertain significance in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-05). Absent from gnomAD; Associated with autosomal recessive hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR c.442+5del?

EDAR c.442+5del is associated with autosomal recessive hypohidrotic ectodermal dysplasia, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (ClinVar).

How common is EDAR c.442+5del in the general population?

EDAR c.442+5del 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.

EDAR c.442+5del

rs2470708552 · VCV2120011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1

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: EDAR
Coding: c.442+5del
MANE Select: NM_022336
dbSNP: rs2470708552
Type: Deletion
Location: chr2:108923363 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB

Full EDAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive hypohidrotic ectodermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant

For Hypohidrotic ectodermal dysplasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

EDAR c.1024+16del Benign ★★ same condition
EDAR p.Asp253fs Pathogenic ★ same condition
EDAR p.Glu311fs Pathogenic ★ same condition
EDAR p.Gly390fs Pathogenic ★ same condition
EDAR p.Leu397_Phe398insTer Pathogenic ★ same condition
EDAR p.Leu412fs Likely pathogenic ★ same condition
EDAR p.Lys328fs Pathogenic ★ same condition
EDAR p.Ser407fs 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/edar-c-442-plus-5del (accessed [today's date]).

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