Is EDAR p.Ser283Arg (c.849C>A) pathogenic?

EDAR p.Ser283Arg (c.849C>A) is classified Uncertain significance in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9328); Absent from gnomAD v4.1; Associated with hypohidrotic ectodermal dysplasia.

What condition is associated with EDAR p.Ser283Arg (c.849C>A)?

EDAR p.Ser283Arg (c.849C>A) is associated with hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Ser283Arg (c.849C>A) in the general population?

EDAR p.Ser283Arg (c.849C>A) is absent from gnomAD v4.1 (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.Ser283Arg (c.849C>A)?

AlphaMissense predicts likely pathogenic (score 0.9328) — an in-silico prediction, not a clinical call.

EDAR p.Ser283Arg

c.849C>A · rs145796324 · VCV894530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9328 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.9328	likely pathogenic
REVEL	0.494	indeterminate
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	8.883	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDAR
Protein: p.Ser283Arg
Coding: c.849C>A
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.Ser283= Benign ★ 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-ser283arg (accessed [today's date]).

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