Is EDA p.Asp129Glu (c.387C>G) pathogenic?

EDA p.Asp129Glu (c.387C>G) is classified Likely benign in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). AlphaMissense: likely benign (0.0794); Very rare (popmax 0.0087%, amr); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Asp129Glu (c.387C>G)?

EDA p.Asp129Glu (c.387C>G) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Asp129Glu (c.387C>G) in the general population?

EDA p.Asp129Glu (c.387C>G) is very rare (popmax 0.0087%, amr) (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.Asp129Glu (c.387C>G)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

EDA p.Asp129Glu

c.387C>G · rs750635386 · VCV2160024

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0087%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.49	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 0.65	GERP 0.033, phastCons 0.78
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	14.67	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 0.0087% Admixed American · 4/45,966 alleles

Filtering AF 0.00293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00177%

Overall 0.000744% 9/1,209,982 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0087%	11,492
African / African-American	0.00699%	14,303
European (non-Finnish)	0.000112%	895,071

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.Asp129Glu
Coding: c.387C>G
MANE Select: NM_001399
dbSNP: rs750635386
Type: single nucleotide variant
Location: chrX:69616695 (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 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-asp129glu (accessed [today's date]).

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