Is EDAR p.Lys81= (c.243A>G) pathogenic?

EDAR p.Lys81= (c.243A>G) is classified Benign/Likely benign in EDAR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.531%, sas); Associated with hypohidrotic ectodermal dysplasia.

How common is EDAR p.Lys81= (c.243A>G) in the general population?

EDAR p.Lys81= (c.243A>G) is rare (popmax 0.531%, sas) (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.Lys81=

Q: What condition is associated with EDAR p.Lys81= (c.243A>G)?

EDAR p.Lys81= (c.243A>G) is associated with hypohidrotic ectodermal dysplasia, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.243A>G · rs145518416 · VCV702817

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.531%, sas)

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 1.5	GERP -0.99, phastCons 1
Overall
CADD	9.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.531% South Asian · 484/91,084 alleles

Filtering AF 0.492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.477%

Overall 0.106% 1,705/1,614,146 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.531%	188
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.171%	584
European (non-Finnish)	0.0892%	1,122
Admixed American	0.0466%	2,144
African / African-American	0.012%	8,337
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Finnishnot grpmax-eligible	0.00625%	15,997
East Asian	0.00223%	44,886

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.Lys81=
Coding: c.243A>G
MANE Select: NM_022336
dbSNP: rs145518416
Type: single nucleotide variant
Location: chr2:108929311 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 81: 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

Also linked: ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant 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 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-lys81 (accessed [today's date]).

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