Is EDAR p.Asp110Ala (c.329A>C) pathogenic?

EDAR p.Asp110Ala (c.329A>C) is classified Pathogenic in EDAR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-06-01). AlphaMissense: likely pathogenic (0.9811); Very rare (popmax 0.000254%, nfe); Associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive.

What condition is associated with EDAR p.Asp110Ala (c.329A>C)?

EDAR p.Asp110Ala (c.329A>C) is associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (ClinVar).

How common is EDAR p.Asp110Ala (c.329A>C) in the general population?

EDAR p.Asp110Ala (c.329A>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about EDAR p.Asp110Ala (c.329A>C)?

AlphaMissense predicts likely pathogenic (score 0.9811) — an in-silico prediction, not a clinical call.

EDAR p.Asp110Ala

c.329A>C · rs121908455 · VCV5856

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.9811	likely pathogenic ✓ concordant with ClinVar · top 9% in EDAR
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -15.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	25.1	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 0.000254% European (non-Finnish) · 3/1,180,040 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,770 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.Asp110Ala
Coding: c.329A>C
MANE Select: NM_022336
dbSNP: rs121908455
Type: single nucleotide variant
Location: chr2:108929225 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 110: a disulfide bond; a UniProt-annotated variant site (in ectd10b)

Full EDAR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDAR p.Asp110Asn Uncertain significance ★★ ⚠ same residue
EDAR p.Asp110= Likely benign ★ same residue
EDAR c.730+1G>T Pathogenic ★★ same condition
EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg89His Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Cys148Arg Likely pathogenic ★★ same condition
EDAR p.Gly382Ser 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-asp110ala (accessed [today's date]).

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