Is EDA p.Val283Met (c.847G>A) pathogenic?

EDA p.Val283Met (c.847G>A) is classified Uncertain significance in EDA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-05-22). AlphaMissense: likely pathogenic (0.8758); Absent from gnomAD v4.1; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Val283Met (c.847G>A)?

EDA p.Val283Met (c.847G>A) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Val283Met (c.847G>A) in the general population?

EDA p.Val283Met (c.847G>A) 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.Val283Met (c.847G>A)?

AlphaMissense predicts likely pathogenic (score 0.8758) — an in-silico prediction, not a clinical call.

EDA p.Val283Met

c.847G>A · VCV4067100

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8758 · 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	0.8758	likely pathogenic
REVEL	0.706	pathogenic-leaning
SaProt	LLR -4.80	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 12	GERP 4.8, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	29.9	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.Val283Met
Coding: c.847G>A
MANE Select: NM_001399
Type: single nucleotide variant
Location: chrX:70033451 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 283: a turn; 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

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.Val283Gly Uncertain significance ★ ⚠ same residue
EDA p.Val283Leu 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
EDA c.924+1G>T 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-val283met (accessed [today's date]).

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