Is EDAR p.Pro52= (c.156G>A) pathogenic?

EDAR p.Pro52= (c.156G>A) is classified Likely benign in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.399%, eas); Associated with hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR p.Pro52= (c.156G>A)?

EDAR p.Pro52= (c.156G>A) is associated with hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Pro52= (c.156G>A) in the general population?

EDAR p.Pro52= (c.156G>A) is rare (popmax 0.399%, 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.Pro52=

c.156G>A · rs3749101 · VCV894157

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.399%, 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 -20	GERP -5
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.399% East Asian · 179/44,864 alleles

Filtering AF 0.351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.333%

Overall 0.0193% 311/1,613,844 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.399%	251
South Asian	0.123%	813
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00333%	30,004
European (non-Finnish)	0.000932%	107,268

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.Pro52=
Coding: c.156G>A
MANE Select: NM_022336
dbSNP: rs3749101
Type: single nucleotide variant
Location: chr2:108930138 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 52: a disulfide bond

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.Pro52Leu Uncertain significance ★★ ⚠ same residue
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

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-pro52 (accessed [today's date]).

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