Is EDAR p.Thr403= (c.1209G>A) pathogenic?

EDAR p.Thr403= (c.1209G>A) is classified Likely benign in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-14). Ultra-rare (popmax 0.033%, mid); Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

How common is EDAR p.Thr403= (c.1209G>A) in the general population?

EDAR p.Thr403= (c.1209G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

EDAR p.Thr403=

Q: What condition is associated with EDAR p.Thr403= (c.1209G>A)?

EDAR p.Thr403= (c.1209G>A) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.1209G>A · rs200198949 · VCV463879

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -20	GERP -3.6
Overall
CADD	0.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00219% 32/1,461,828 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
East Asian	0.00446%	22,438
Admixed American	0.00333%	30,010
European (non-Finnish)	0.00212%	47,201
South Asian	0.0011%	91,054

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.Thr403=
Coding: c.1209G>A
MANE Select: NM_022336
dbSNP: rs200198949
Type: single nucleotide variant
Location: chr2:108897045 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 403: a UniProt-annotated variant site (in ectd10b); the death domain

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.Thr403Arg Likely pathogenic ★ ⚠ same residue
EDAR p.Thr403Met Pathogenic ★ ⚠ same residue
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

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-thr403 (accessed [today's date]).

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