Is EDA p.217PGP[2] (c.660_668del) pathogenic?

EDA p.217PGP[2] (c.660668del) is classified Conflicting classifications of pathogenicity in EDA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-14). Very rare (popmax 0.00229%, amr); Associated with Inborn genetic diseases.

What condition is associated with EDA p.217PGP[2] (c.660_668del)?

EDA p.217PGP[2] (c.660_668del) is associated with Inborn genetic diseases, X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.217PGP[2] (c.660_668del) in the general population?

EDA p.217PGP[2] (c.660_668del) is very rare (popmax 0.00229%, amr) (gnomAD).

EDA p.217PGP[2]

c.660_668del · rs1326976532 · VCV2716467

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00229%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.8	GERP -8
Overall
CADD	19.67	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GGACCCCCTGGTCCTCCA simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% Admixed American · 1/43,665 alleles

Filtering AF 0.000106% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000588% 7/1,191,131 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00427%	23,436
Admixed Americangrpmax	0.00229%	43,665
European (non-Finnish)	0.000451%	221,527

Remaining individuals 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.217PGP[2]
Coding: c.660_668del
MANE Select: NM_001399
dbSNP: rs1326976532
Type: Deletion
Location: chrX:70027982 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB

Full EDA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked hypohidrotic ectodermal dysplasia

Similar variants

EDA p.202_204IPG[1] Pathogenic/Likely pathogenic ★★ same condition
EDA p.217_219PGP[1] Pathogenic ★★ same condition
EDA p.Ala166fs Pathogenic ★★ same condition
EDA p.Asn185_Pro196del Pathogenic ★★ same condition
EDA p.Gly85fs Pathogenic ★★ same condition
EDA p.Phe317fs Pathogenic ★★ same condition
EDA p.Pro199fs Pathogenic ★★ same condition
EDA p.Pro219_Gly230del Pathogenic/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-217pgp-2 (accessed [today's date]).

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