Is EDA p.Pro118= (c.354G>A) pathogenic?

EDA p.Pro118= (c.354G>A) is classified Likely benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). Very rare (popmax 0.00434%, amr); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Pro118= (c.354G>A)?

EDA p.Pro118= (c.354G>A) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Pro118= (c.354G>A) in the general population?

EDA p.Pro118= (c.354G>A) is very rare (popmax 0.00434%, 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 p.Pro118=

c.354G>A · rs762842929 · VCV2188388

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00434%, 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -3
Overall
CADD	2.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00434% Admixed American · 2/46,126 alleles

Filtering AF 0.000719% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000269%

Overall 0.000455% 5/1,098,157 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00434%	23,063
East Asian	0.00296%	33,761
South Asian	0.00176%	56,963
African / African-American	0.00173%	57,825

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.Pro118=
Coding: c.354G>A
MANE Select: NM_001399
dbSNP: rs762842929
Type: single nucleotide variant
Location: chrX:69616662 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 118: a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation); the 'disordered' region

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-pro118 (accessed [today's date]).

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