Is EDA p.Leu266= (c.798T>C) pathogenic?

EDA p.Leu266= (c.798T>C) is classified Conflicting classifications of pathogenicity in EDA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-24). Absent from gnomAD v4.1; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Leu266= (c.798T>C)?

EDA p.Leu266= (c.798T>C) is associated with X-linked hypohidrotic ectodermal dysplasia, asphyxiating thoracic dystrophy 3 (ClinVar).

How common is EDA p.Leu266= (c.798T>C) in the general population?

EDA p.Leu266= (c.798T>C) is absent from gnomAD v4.1 (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.Leu266=

c.798T>C · rs2147516257 · VCV1334471

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 4.8, phastCons 1
Overall
CADD	15.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDA
Protein: p.Leu266=
Coding: c.798T>C
MANE Select: NM_001399
dbSNP: rs2147516257
Type: single nucleotide variant
Location: chrX:70033402 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 266: an α-helix; 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

Also linked: asphyxiating thoracic dystrophy 3

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.Leu266Phe Uncertain significance ★ ⚠ same residue
EDA p.Leu266Pro Uncertain significance ★ ⚠ same residue
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
EDA c.924+1G>T 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-leu266 (accessed [today's date]).

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