Is EDA p.His124Arg (c.371A>G) pathogenic?

EDA p.His124Arg (c.371A>G) is classified Likely benign in EDA (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-05). AlphaMissense: likely benign (0.0563); Ultra-rare (popmax 0.0317%, sas); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.His124Arg (c.371A>G)?

EDA p.His124Arg (c.371A>G) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.His124Arg (c.371A>G) in the general population?

EDA p.His124Arg (c.371A>G) is ultra-rare (popmax 0.0317%, sas) (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.His124Arg (c.371A>G)?

AlphaMissense predicts likely benign (score 0.0563) — an in-silico prediction, not a clinical call.

EDA p.His124Arg

c.371A>G · rs751470511 · VCV1113123

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0563 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.0563	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -5.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.18, phastCons 0.86
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	13.8	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 0.0317% South Asian · 18/56,851 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.00164% 18/1,098,133 alleles · ultra-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.His124Arg
Coding: c.371A>G
MANE Select: NM_001399
dbSNP: rs751470511
Type: single nucleotide variant
Location: chrX:69616679 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 124: 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 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
EDA p.Ala349Thr 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-his124arg (accessed [today's date]).

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