Is EDAR p.Ser19= (c.57T>A) pathogenic?

EDAR p.Ser19= (c.57T>A) is classified Benign in EDAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). Low-frequency (popmax 2.58%, afr); Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

What condition is associated with EDAR p.Ser19= (c.57T>A)?

EDAR p.Ser19= (c.57T>A) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Ser19= (c.57T>A) in the general population?

EDAR p.Ser19= (c.57T>A) is low-frequency (popmax 2.58%, afr) (gnomAD).

EDAR p.Ser19=

c.57T>A · rs28407350 · VCV532548

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.58%, afr)

Conditions

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

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 -1	GERP -5
Overall
CADD	0.603	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.58% African / African-American · 1,939/75,022 alleles

Filtering AF 2.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.45%

Overall 0.136% 2,190/1,614,074 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.58%	39
Remaining individualsnot grpmax-eligible	0.192%	521
Middle Eastern	0.181%	551
Admixed American	0.135%	741
South Asian	0.00439%	22,770
European (non-Finnish)	0.00297%	33,715

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.Ser19=
Coding: c.57T>A
MANE Select: NM_022336
dbSNP: rs28407350
Type: single nucleotide variant
Location: chr2:108930237 (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

ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive hypohidrotic ectodermal dysplasia

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-ser19 (accessed [today's date]).

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