Is EDA p.Arg156Ser (c.466_467delinsTC) pathogenic?

EDA p.Arg156Ser (c.466467delinsTC) is classified Uncertain significance in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). Absent from gnomAD; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg156Ser (c.466_467delinsTC)?

EDA p.Arg156Ser (c.466_467delinsTC) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg156Ser (c.466_467delinsTC) in the general population?

EDA p.Arg156Ser (c.466_467delinsTC) is absent from gnomAD (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.Arg156Ser

c.466_467delinsTC · rs2520242754 · VCV2026580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EDA
Protein: p.Arg156Ser
Coding: c.466_467delinsTC
MANE Select: NM_001399
dbSNP: rs2520242754
Type: Indel
Location: chrX:69957096 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 156: a UniProt-annotated variant site (in xhed; abolishes proteolytic processing); a UniProt-annotated variant site (in xhed); 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 p.Arg156Cys Pathogenic/Likely pathogenic ★★ same residue
EDA p.Arg156His Pathogenic ★★ ⚠ same residue
EDA p.Arg156Leu Pathogenic ★ same residue
EDA c.585_706+6delinsTCCTCCTGGTCC Pathogenic ★ same condition
EDA p.Ala367fs Pathogenic ★ same condition
EDA p.Gly2fs Likely pathogenic ★ same condition
EDA p.Leu296fs Likely pathogenic ★ same condition
EDA p.Leu78fs 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-arg156ser (accessed [today's date]).

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