Is EDA p.Asp368= (c.1104C>T) pathogenic?

EDA p.Asp368= (c.1104C>T) is classified Benign/Likely benign in EDA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.783%, sas); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Asp368= (c.1104C>T)?

EDA p.Asp368= (c.1104C>T) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Asp368= (c.1104C>T) in the general population?

EDA p.Asp368= (c.1104C>T) is rare (popmax 0.783%, sas) (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.Asp368=

c.1104C>T · rs150292516 · VCV706925

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.783%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 4.7, phastCons 1
Overall
CADD	8.966	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.783% South Asian · 442/56,474 alleles

Filtering AF 0.722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.699%

Overall 0.0391% 472/1,205,743 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.783%	128
Remaining individualsnot grpmax-eligible	0.0484%	2,067
Middle Eastern	0.023%	4,350
East Asian	0.00297%	33,623
Admixed American	0.00222%	44,981
European (non-Finnish)	0.000447%	223,550

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.Asp368=
Coding: c.1104C>T
MANE Select: NM_001399
dbSNP: rs150292516
Type: single nucleotide variant
Location: chrX:70035537 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 368: 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 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
EDA p.Ala349Ser Likely pathogenic ★★ ⚠ same condition
EDA p.Ala349Thr 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-asp368 (accessed [today's date]).

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