Is EDAR p.Ser250= (c.750C>T) pathogenic?

EDAR p.Ser250= (c.750C>T) is classified Benign in EDAR (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive hypohidrotic ectodermal dysplasia.

How is Hypohidrotic ectodermal dysplasia inherited?

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

EDAR p.Ser250=

Q: What condition is associated with EDAR p.Ser250= (c.750C>T)?

EDAR p.Ser250= (c.750C>T) is associated with autosomal recessive hypohidrotic ectodermal dysplasia, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (ClinVar).

Q: How common is EDAR p.Ser250= (c.750C>T) in the general population?

EDAR p.Ser250= (c.750C>T) is common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.750C>T · rs260632 · VCV155870

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele

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 -7.3	GERP -4.6
Overall
CADD	0.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99.9% East Asian · 44,767/44,824 alleles

Filtering AF 99.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.8%

Overall 90.7% 1,463,421/1,613,114 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	99.9%	1
Admixed American	94.6%	1
Ashkenazi Jewishnot grpmax-eligible	94.1%	1
Middle Eastern	92.5%	1
South Asian	92%	1
Remaining individualsnot grpmax-eligible	91.4%	1
Finnishnot grpmax-eligible	90.3%	1
European (non-Finnish)	90.1%	1
African / African-American	88.3%	1
Amishnot grpmax-eligible	78%	1

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.Ser250=
Coding: c.750C>T
MANE Select: NM_022336
dbSNP: rs260632
Type: single nucleotide variant
Location: chr2:108910513 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 250: the 'disordered' region

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 ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive 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 c.730+1G>T Pathogenic ★★ same condition
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.Cys148Arg 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-ser250 (accessed [today's date]).

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