Is EDA p.Arg20= (c.60A>C) pathogenic?

EDA p.Arg20= (c.60A>C) is classified Benign/Likely benign in EDA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-11). Ultra-rare (popmax 0.0243%, nfe); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg20= (c.60A>C)?

EDA p.Arg20= (c.60A>C) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg20= (c.60A>C) in the general population?

EDA p.Arg20= (c.60A>C) is ultra-rare (popmax 0.0243%, 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.Arg20=

c.60A>C · rs183801635 · VCV1169967

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, 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 1.9	GERP -0.65, phastCons 1
Overall
CADD	6.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0243% European (non-Finnish) · 217/894,471 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.0317% 382/1,206,729 alleles · ultra-rare exomes 348/1,093,937 · genomes 34/112,792 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.348%	287
European (non-Finnish)grpmax	0.0243%	4,122
Remaining individualsnot grpmax-eligible	0.0105%	9,498
African / African-American	0.00869%	11,508
Admixed American	0.00218%	45,956

Finnish 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.Arg20=
Coding: c.60A>C
MANE Select: NM_001399
dbSNP: rs183801635
Type: single nucleotide variant
Location: chrX:69616368 (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.Arg20Ter 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-arg20 (accessed [today's date]).

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