Is EDAR p.Ser283= (c.849C>T) pathogenic?

EDAR p.Ser283= (c.849C>T) is classified Benign in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.333%, afr); Associated with hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR p.Ser283= (c.849C>T)?

EDAR p.Ser283= (c.849C>T) is associated with hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Ser283= (c.849C>T) in the general population?

EDAR p.Ser283= (c.849C>T) is rare (popmax 0.333%, afr) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

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

EDAR p.Ser283=

c.849C>T · rs145796324 · VCV894529

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.333%, afr)

Conditions

hypohidrotic ectodermal dysplasia

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 -0.49	GERP -5.5, phastCons 0.001
Overall
CADD	1.125	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.333% African / African-American · 250/75,014 alleles

Filtering AF 0.299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.286%

Overall 0.02% 323/1,612,446 alleles · rare exomes 191/1,460,244 · genomes 132/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.333%	300
Middle Eastern	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.0224%	4,462
Admixed American	0.02%	4,999
European (non-Finnish)	0.00373%	26,794
South Asian	0.0011%	91,066

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.Ser283=
Coding: c.849C>T
MANE Select: NM_022336
dbSNP: rs145796324
Type: single nucleotide variant
Location: chr2:108907974 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 283: the 'disordered' region

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.Ser283Arg Uncertain significance ★ ⚠ same residue
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

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-ser283 (accessed [today's date]).

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