Is EDAR p.Phe381= (c.1143C>T) pathogenic?

EDAR p.Phe381= (c.1143C>T) is classified Benign in EDAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). Rare (popmax 0.351%, afr); Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

How common is EDAR p.Phe381= (c.1143C>T) in the general population?

EDAR p.Phe381= (c.1143C>T) is rare (popmax 0.351%, afr) (gnomAD).

EDAR p.Phe381=

Q: What condition is associated with EDAR p.Phe381= (c.1143C>T)?

EDAR p.Phe381= (c.1143C>T) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.1143C>T · rs143639120 · VCV707603

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.351%, afr)

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 -1.1	GERP -3.9
Overall
CADD	8.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.351% African / African-American · 263/75,020 alleles

Filtering AF 0.316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.302%

Overall 0.0223% 360/1,614,028 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.351%	285
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.0133%	7,500
East Asian	0.00669%	14,955
European (non-Finnish)	0.00576%	17,353

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.Phe381=
Coding: c.1143C>T
MANE Select: NM_006267 · reported on NM_022336
dbSNP: rs143639120
Type: single nucleotide variant
Location: chr2:108897111 (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-phe381 (accessed [today's date]).

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