Is EDA p.Val365Met (c.1093G>A) pathogenic?

EDA p.Val365Met (c.1093G>A) is classified Likely pathogenic in EDA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-22). AlphaMissense: likely pathogenic (0.8986); Very rare (popmax 0.000112%, nfe); Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Val365Met (c.1093G>A)?

EDA p.Val365Met (c.1093G>A) is associated with X-linked hypohidrotic ectodermal dysplasia, tooth agenesis, selective, X-linked, 1 (ClinVar).

How common is EDA p.Val365Met (c.1093G>A) in the general population?

EDA p.Val365Met (c.1093G>A) is very rare (popmax 0.000112%, nfe) (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.Val365Met (c.1093G>A)?

AlphaMissense predicts likely pathogenic (score 0.8986) — an in-silico prediction, not a clinical call.

EDA p.Val365Met

c.1093G>A · rs2147519270 · VCV1482275

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.8986	likely pathogenic ✓ concordant with ClinVar
REVEL	0.702	pathogenic-leaning
SaProt	LLR -7.53	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 9.7	GERP 4.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	28.2	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 0.000112% European (non-Finnish) · 1/894,901 alleles

Overall 9.11e-05% 1/1,098,053 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.Val365Met
Coding: c.1093G>A
MANE Select: NM_001399
dbSNP: rs2147519270
Type: single nucleotide variant
Location: chrX:70035526 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 365: 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: tooth agenesis, selective, X-linked, 1

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.Val365Ala Pathogenic/Likely pathogenic ★★ ⚠ 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-val365met (accessed [today's date]).

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