Is EDA c.741+9G>A pathogenic?

EDA c.741+9G>A is classified Benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-28). Ultra-rare (popmax 0.0282%, amr); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA c.741+9G>A?

EDA c.741+9G>A is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA c.741+9G>A in the general population?

EDA c.741+9G>A is ultra-rare (popmax 0.0282%, amr) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

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

EDA c.741+9G>A

rs751258727 · VCV1166394

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, amr)

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.32 · evaluated, not missing
Pangolin	Δ0.35	gain · loss 0.17 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 1.9	GERP 0.23, phastCons 1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	12.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0282% Admixed American · 13/46,114 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.00264% 29/1,097,017 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0282%	3,547
Remaining individualsnot grpmax-eligible	0.0042%	23,812
European (non-Finnish)	0.00157%	63,894

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
Coding: c.741+9G>A
MANE Select: NM_001399
dbSNP: rs751258727
Type: single nucleotide variant
Location: chrX:70029547 (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 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-c-741-plus-9g-a (accessed [today's date]).

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