Is EDA p.Pro145= (c.435A>G) pathogenic?

EDA p.Pro145= (c.435A>G) is classified Benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Ultra-rare (popmax 0.0115%, nfe); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Pro145= (c.435A>G)?

EDA p.Pro145= (c.435A>G) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Pro145= (c.435A>G) in the general population?

EDA p.Pro145= (c.435A>G) is ultra-rare (popmax 0.0115%, nfe) (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.Pro145=

c.435A>G · rs146844463 · VCV1170040

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0115%, nfe)

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 2.1	GERP -3.1, phastCons 1
Overall
CADD	6.533	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0115% European (non-Finnish) · 103/895,245 alleles

Filtering AF 0.00965% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00901%

Overall 0.00909% 110/1,210,519 alleles · ultra-rare exomes 95/1,097,912 · genomes 15/112,607 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0115%	8,692
Remaining individualsnot grpmax-eligible	0.0084%	11,901
African / African-American	0.00522%	19,154

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.Pro145=
Coding: c.435A>G
MANE Select: NM_001399
dbSNP: rs146844463
Type: single nucleotide variant
Location: chrX:69957065 (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.Pro145fs Likely pathogenic ★ 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
EDA p.Ala349Ser 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-pro145 (accessed [today's date]).

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