Is EDAR p.Leu412fs (c.1234del) pathogenic?

EDAR p.Leu412fs (c.1234del) is classified Likely pathogenic in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

What condition is associated with EDAR p.Leu412fs (c.1234del)?

EDAR p.Leu412fs (c.1234del) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant (ClinVar).

EDAR p.Leu412fs

c.1234del · VCV4073582

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: EDAR
Protein: p.Leu412fs
Coding: c.1234del
MANE Select: NM_022336
Type: Deletion
Location: chr2:108897020 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 412: the death domain

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

Disease context

ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDAR p.Leu412Phe Uncertain significance ★ ⚠ same residue
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.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-p-leu412fs (accessed [today's date]).

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