Is EDA c.924+219T>A pathogenic?

EDA c.924+219T>A is classified Benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-12). Common (popmax 15.6%, mid) — too common for a highly-penetrant pathogenic allele.

EDA c.924+219T>A

Q: How common is EDA c.924+219T>A in the general population?

EDA c.924+219T>A is common (popmax 15.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs147910377 · VCV1294829

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 15.6%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +219	deep intronic (+219 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 2.6, phastCons 0.41
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	9.878	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.6% Middle Eastern · 34/218 alleles

Filtering AF 13.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.2%

Overall 9.51% 10,503/110,496 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	19%	5
Middle Easterngrpmax	15.6%	6
European (non-Finnish)	13.6%	7
South Asian	10.5%	10
Remaining individualsnot grpmax-eligible	10.2%	10
Amishnot grpmax-eligible	9.72%	10
Admixed American	8.41%	12
Finnishnot grpmax-eligible	7.52%	13
African / African-American	3.3%	30
East Asian	0.0573%	1,744

Ashkenazi Jewish 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
Coding: c.924+219T>A
MANE Select: NM_001399
dbSNP: rs147910377
Type: single nucleotide variant
Location: chrX:70033747 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB

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

Similar variants

EDA c.526+2T>C Pathogenic/Likely pathogenic ★★ same type
EDA c.526+5G>T Likely pathogenic ★★ same type
EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.706+1G>A Pathogenic/Likely pathogenic ★★ same type
EDA c.707-13T>G Pathogenic ★★ same type
EDA c.742-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.924+1G>T Likely pathogenic ★★ same type
EDA p.Ala349Ser Likely pathogenic ★★ same type

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-924-plus-219t-a (accessed [today's date]).

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