Is EDA p.Gln197Lys (c.589C>A) pathogenic?

EDA p.Gln197Lys (c.589C>A) is classified Uncertain significance in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-09). AlphaMissense: ambiguous (0.5079); Absent from gnomAD v4.1; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Gln197Lys (c.589C>A)?

EDA p.Gln197Lys (c.589C>A) is associated with X-linked hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDA p.Gln197Lys (c.589C>A) in the general population?

EDA p.Gln197Lys (c.589C>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.Gln197Lys (c.589C>A)?

AlphaMissense predicts ambiguous (score 0.5079) — an in-silico prediction, not a clinical call.

EDA p.Gln197Lys

c.589C>A · VCV4743588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5079 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,176,570)

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.5079	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -9.64	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 3.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	22.9	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

No allele count reported in gnomAD v4.1 (AN 1,176,570). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EDA
Protein: p.Gln197Lys
Coding: c.589C>A
MANE Select: NM_001399
Type: single nucleotide variant
Location: chrX:70027919 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 197: the collagen-like domain; a UniProt-annotated variant site (in xhed); a UniProt-annotated variant site (in xhed; uncertain significance); 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 p.Gln197fs 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-gln197lys (accessed [today's date]).

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