Is EDA p.Arg33Trp (c.97C>T) pathogenic?

EDA p.Arg33Trp (c.97C>T) is classified Conflicting classifications of pathogenicity in EDA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1602); Very rare (popmax 0.00296%, eas); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Arg33Trp (c.97C>T)?

EDA p.Arg33Trp (c.97C>T) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Arg33Trp (c.97C>T) in the general population?

EDA p.Arg33Trp (c.97C>T) is very rare (popmax 0.00296%, eas) (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.Arg33Trp (c.97C>T)?

AlphaMissense predicts likely benign (score 0.1602) — an in-silico prediction, not a clinical call.

EDA p.Arg33Trp

c.97C>T · rs1168030930 · VCV583287

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.1602	likely benign
REVEL	0.506	indeterminate
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 145 bp · p 0.075 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.00296% East Asian · 1/33,775 alleles

Overall 9.14e-05% 1/1,093,747 alleles · very rare

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.Arg33Trp
Coding: c.97C>T
MANE Select: NM_001399
dbSNP: rs1168030930
Type: single nucleotide variant
Location: chrX:69616405 (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.Arg33= Likely benign ★ 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-arg33trp (accessed [today's date]).

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