Is EDAR p.Asp430Asn (c.1288G>A) pathogenic?

EDAR p.Asp430Asn (c.1288G>A) is classified Uncertain significance in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: ambiguous (0.5041); Very rare (popmax 0.00223%, eas); Associated with hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR p.Asp430Asn (c.1288G>A)?

EDAR p.Asp430Asn (c.1288G>A) is associated with hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Asp430Asn (c.1288G>A) in the general population?

EDAR p.Asp430Asn (c.1288G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

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

What do computational predictors say about EDAR p.Asp430Asn (c.1288G>A)?

AlphaMissense predicts ambiguous (score 0.5041) — an in-silico prediction, not a clinical call.

EDAR p.Asp430Asn

c.1288G>A · rs886054744 · VCV330705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.5041	ambiguous
REVEL	0.543	indeterminate
SaProt	LLR -7.99	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,856 alleles

Overall 6.84e-05% 1/1,461,402 alleles · very rare

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.Asp430Asn
Coding: c.1288G>A
MANE Select: NM_022336
dbSNP: rs886054744
Type: single nucleotide variant
Location: chr2:108896966 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 430: the death domain

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

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.Ala187Val Uncertain significance ★★ ⚠ same condition
EDAR p.Pro225Leu Uncertain significance ★★ ⚠ same condition
EDAR p.Ser268Cys Uncertain significance ★★ ⚠ same condition
EDAR p.Val203Ile Uncertain significance ★★ ⚠ same condition
EDAR c.357-4G>A Benign/Likely benign ★★ same condition
EDAR c.*1129A>G Benign ★★ same condition
EDAR c.*1133C>T Benign ★★ same condition
EDAR c.*1248G>T Benign/Likely benign ★★ 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-asp430asn (accessed [today's date]).

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