Is EDA p.Tyr61His (c.181T>C) pathogenic?

EDA p.Tyr61His (c.181T>C) is classified Pathogenic/Likely pathogenic in EDA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-09). AlphaMissense: likely pathogenic (0.8612); Absent from gnomAD v4.1; Associated with X-linked hypohidrotic ectodermal dysplasia.

What condition is associated with EDA p.Tyr61His (c.181T>C)?

EDA p.Tyr61His (c.181T>C) is associated with X-linked hypohidrotic ectodermal dysplasia, tooth agenesis, selective, X-linked, 1 (ClinVar).

How common is EDA p.Tyr61His (c.181T>C) in the general population?

EDA p.Tyr61His (c.181T>C) 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.Tyr61His (c.181T>C)?

AlphaMissense predicts likely pathogenic (score 0.8612) — an in-silico prediction, not a clinical call.

EDA p.Tyr61His

c.181T>C · rs132630308 · VCV11031

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8612 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

X-linked hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.8612	likely pathogenic ✓ concordant with ClinVar
REVEL	0.866	moderately pathogenic-leaning
SaProt	LLR -11.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	24.2	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

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.Tyr61His
Coding: c.181T>C
MANE Select: NM_001399
dbSNP: rs132630308
Type: single nucleotide variant
Location: chrX:69616489 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 61: a UniProt-annotated variant site (in xhed)

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.Tyr61Asn Likely pathogenic ★ same residue
EDA p.Tyr61Ter Pathogenic ★ same residue
EDA p.Tyr61= Likely benign ★ 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

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-tyr61his (accessed [today's date]).

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