Is EDAR p.Tyr69= (c.207C>T) pathogenic?

EDAR p.Tyr69= (c.207C>T) is classified Benign/Likely benign in EDAR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-19). Rare (popmax 0.878%, sas); Associated with autosomal recessive hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR p.Tyr69= (c.207C>T)?

EDAR p.Tyr69= (c.207C>T) is associated with autosomal recessive hypohidrotic ectodermal dysplasia, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Tyr69= (c.207C>T) in the general population?

EDAR p.Tyr69= (c.207C>T) is rare (popmax 0.878%, sas) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

EDAR p.Tyr69=

c.207C>T · rs147059377 · VCV155866

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.878%, sas)

Conditions

autosomal recessive hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -4.9
Overall
CADD	0.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.878% South Asian · 800/91,084 alleles

Filtering AF 0.828% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.808%

Overall 0.0737% 1,190/1,614,132 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.878%	114
Middle Eastern	0.264%	379
Remaining individualsnot grpmax-eligible	0.0752%	1,330
Admixed American	0.0267%	3,752
European (non-Finnish)	0.0254%	3,933
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
African / African-American	0.008%	12,506
Finnishnot grpmax-eligible	0.00156%	63,980

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: EDAR
Protein: p.Tyr69=
Coding: c.207C>T
MANE Select: NM_022336
dbSNP: rs147059377
Type: single nucleotide variant
Location: chr2:108929347 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 69: a disulfide bond

Full EDAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive hypohidrotic ectodermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant hypohidrotic ectodermal dysplasia

For Hypohidrotic ectodermal dysplasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg25Ter Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Arg358Ter Pathogenic ★★ same condition
EDAR p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Arg89His Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Cys301Ter Pathogenic ★★ same condition
EDAR p.Cys428Arg 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/edar-p-tyr69 (accessed [today's date]).

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