Is EDAR p.Ile202= (c.606C>T) pathogenic?

EDAR p.Ile202= (c.606C>T) is classified Uncertain significance in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0802%, eas); Associated with hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR p.Ile202= (c.606C>T)?

EDAR p.Ile202= (c.606C>T) is associated with hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Ile202= (c.606C>T) in the general population?

EDAR p.Ile202= (c.606C>T) is ultra-rare (popmax 0.0802%, eas) (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.Ile202=

c.606C>T · rs201950451 · VCV893316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, eas)

Conditions

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 -7	GERP -4.9
Overall
CADD	1.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0802% East Asian · 36/44,866 alleles

Filtering AF 0.0595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00248% 40/1,614,160 alleles · ultra-rare exomes 38/1,461,876 · genomes 2/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0802%	1,246
European (non-Finnish)	0.000339%	295,003

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.Ile202=
Coding: c.606C>T
MANE Select: NM_022336
dbSNP: rs201950451
Type: single nucleotide variant
Location: chr2:108910996 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB

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

Disease context

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

EDAR p.Ala187Val Uncertain significance ★★ ⚠ same condition
EDAR p.Pro225Leu Uncertain significance ★★ ⚠ same condition
EDAR p.Ser268Cys Uncertain significance ★★ ⚠ same condition
EDAR p.Val203Ile Uncertain significance ★★ ⚠ same condition
EDAR c.357-4G>A Benign/Likely benign ★★ same condition
EDAR c.*1129A>G Benign ★★ same condition
EDAR c.*1133C>T Benign ★★ same condition
EDAR c.*1248G>T Benign/Likely benign ★★ 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-ile202 (accessed [today's date]).

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