Is EDAR p.Ser274= (c.822C>A) pathogenic?

EDAR p.Ser274= (c.822C>A) is classified Benign/Likely benign in EDAR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-04). Common (popmax 6.82%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

What condition is associated with EDAR p.Ser274= (c.822C>A)?

EDAR p.Ser274= (c.822C>A) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, hypohidrotic ectodermal dysplasia, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

EDAR p.Ser274=

Q: How common is EDAR p.Ser274= (c.822C>A) in the general population?

EDAR p.Ser274= (c.822C>A) is common (popmax 6.82%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.822C>A · rs79648056 · VCV261573

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 6.82%, afr) — too common for a highly-penetrant pathogenic allele

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 -5.3	GERP -5.5
Overall
CADD	0.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.82% African / African-American · 5,112/74,938 alleles

Filtering AF 6.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.6%

Overall 0.36% 5,790/1,609,768 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.82%	15
Admixed American	0.535%	187
Remaining individualsnot grpmax-eligible	0.462%	216
Middle Eastern	0.297%	336
South Asian	0.00769%	13,001
European (non-Finnish)	0.00374%	26,743

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.Ser274=
Coding: c.822C>A
MANE Select: NM_022336
dbSNP: rs79648056
Type: single nucleotide variant
Location: chr2:108908001 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 274: the 'disordered' region

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: hypohidrotic ectodermal dysplasia 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-ser274 (accessed [today's date]).

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