Is EDA p.Glu19Ala (c.56A>C) pathogenic?

EDA p.Glu19Ala (c.56A>C) is classified Likely benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-22). AlphaMissense: likely benign (0.0941); Very rare (popmax 0.00402%, nfe); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Glu19Ala (c.56A>C)?

EDA p.Glu19Ala (c.56A>C) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Glu19Ala (c.56A>C) in the general population?

EDA p.Glu19Ala (c.56A>C) is very rare (popmax 0.00402%, nfe) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EDA p.Glu19Ala (c.56A>C)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

EDA p.Glu19Ala

c.56A>C · rs752730106 · VCV1597827

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 145 bp · p 0.075 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% European (non-Finnish) · 36/894,455 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00261%

Overall 0.00315% 38/1,206,268 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00421%	23,727
European (non-Finnish)grpmax	0.00402%	24,846

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EDA
Protein: p.Glu19Ala
Coding: c.56A>C
MANE Select: NM_001399
dbSNP: rs752730106
Type: single nucleotide variant
Location: chrX:69616364 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB

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.Glu19= Likely benign ★ same residue
EDA p.Glu19Gly 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-glu19ala (accessed [today's date]).

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