Is EDAR p.Ala435= (c.1305G>A) pathogenic?

EDAR p.Ala435= (c.1305G>A) is classified Benign in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). Rare (popmax 0.711%, amr); Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

How common is EDAR p.Ala435= (c.1305G>A) in the general population?

EDAR p.Ala435= (c.1305G>A) is rare (popmax 0.711%, amr) (gnomAD).

EDAR p.Ala435=

Q: What condition is associated with EDAR p.Ala435= (c.1305G>A)?

EDAR p.Ala435= (c.1305G>A) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.1305G>A · rs564195922 · VCV703304

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.711%, amr)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -3.6
Overall
CADD	0.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.711% Admixed American · 426/59,930 alleles

Filtering AF 0.655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.633%

Overall 0.027% 435/1,613,350 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.711%	141
Remaining individualsnot grpmax-eligible	0.0048%	20,817
African / African-American	0.00267%	37,507
East Asian	0.00223%	44,822
South Asian	0.0022%	45,432
European (non-Finnish)	8.48e-05%	1,179,768

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.Ala435=
Coding: c.1305G>A
MANE Select: NM_006267 · reported on NM_022336
dbSNP: rs564195922
Type: single nucleotide variant
Location: chr2:108896949 (GRCh38)

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

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-ala435 (accessed [today's date]).

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