Is EDA p.Arg276Cys (c.826C>T) pathogenic?

EDA p.Arg276Cys (c.826C>T) is classified Pathogenic/Likely pathogenic in EDA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.7363); Absent from gnomAD v4.1; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg276Cys (c.826C>T)?

EDA p.Arg276Cys (c.826C>T) is associated with X-linked hypohidrotic ectodermal dysplasia, ectodermal dysplasia syndrome (ClinVar).

How common is EDA p.Arg276Cys (c.826C>T) in the general population?

EDA p.Arg276Cys (c.826C>T) is absent from gnomAD v4.1 (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EDA p.Arg276Cys (c.826C>T)?

AlphaMissense predicts likely pathogenic (score 0.7363) — an in-silico prediction, not a clinical call.

EDA p.Arg276Cys

c.826C>T · rs387907197 · VCV31908

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.7363	likely pathogenic ✓ concordant with ClinVar
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 4.8, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDA
Protein: p.Arg276Cys
Coding: c.826C>T
MANE Select: NM_001399
dbSNP: rs387907197
Type: single nucleotide variant
Location: chrX:70033430 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 276: a β-strand; the thd domain

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

Also linked: ectodermal dysplasia syndrome

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.Arg276Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
EDA p.Arg276Gly Likely pathogenic ★ ⚠ same residue
EDA p.Arg276Pro Uncertain significance ★ ⚠ 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

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-arg276cys (accessed [today's date]).

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