Is EDAR p.Gly83Asp (c.248G>A) pathogenic?

EDAR p.Gly83Asp (c.248G>A) is classified Uncertain significance in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: ambiguous (0.4484); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with EDAR p.Gly83Asp (c.248G>A)?

EDAR p.Gly83Asp (c.248G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EDAR p.Gly83Asp (c.248G>A) in the general population?

EDAR p.Gly83Asp (c.248G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about EDAR p.Gly83Asp (c.248G>A)?

AlphaMissense predicts ambiguous (score 0.4484) — an in-silico prediction, not a clinical call.

EDAR p.Gly83Asp

c.248G>A · VCV4246520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4484	ambiguous
REVEL	0.634	indeterminate
SaProt	LLR -8.32	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	24.9	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 0.00133% African / African-American · 1/74,922 alleles

Overall 0.000657% 1/152,194 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.Gly83Asp
Coding: c.248G>A
MANE Select: NM_022336
Type: single nucleotide variant
Location: chr2:108929306 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 83: a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Glu35Lys Uncertain significance ★★ ⚠ same condition
EDAR p.Gly321Arg Uncertain significance ★★ ⚠ same condition
EDAR p.Ala174Val Uncertain significance ★ ⚠ same condition
EDAR p.Ala217Ser Uncertain significance ★ ⚠ same condition
EDAR p.Ala260Val Uncertain significance ★ ⚠ same condition
EDAR p.Ala423Thr Uncertain significance ★ ⚠ same condition
EDAR p.Ala99Thr Uncertain significance ★ ⚠ 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-gly83asp (accessed [today's date]).

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