EDARADD p.Arg208=
c.624T>C · VCV4945699
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0334%, eas)
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 -2.4 | GERP -3.5 |
| Overall | ||
| CADD | 1.493 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0334%
East Asian · 15/44,888 alleles
Filtering AF
0.0206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0166%
Overall
0.00155%
25/1,612,012 alleles · ultra-rare
exomes 22/1,459,860 · genomes 3/152,152 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0334% | 2,993 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,903 |
| South Asian | 0.0011% | 91,002 |
| European (non-Finnish) | 0.000169% | 590,012 |
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
- EDARADD
- Protein
- p.Arg208=
- Coding
- c.624T>C
- MANE Select
- NM_145861
- Type
- single nucleotide variant
- Location
- chr1:236482625 (GRCh38)
- Gene constraint
- LOEUF 0.991 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.81
Similar variants
- EDARADD p.Arg208His Uncertain significance ★ ⚠ same residue
- EDARADD p.Arg66Ter Pathogenic ★★ same type
- EDARADD c.*1962C>T Uncertain significance ★★ same type
- EDARADD c.*863C>T Uncertain significance ★★ same type
- EDARADD p.Arg170Gln Uncertain significance ★★ ⚠ same type
- EDARADD p.Arg196His Uncertain significance ★★ ⚠ same type
- EDARADD p.Asp120His Uncertain significance ★★ ⚠ same type
- EDARADD p.Gln8Glu Uncertain significance ★★ ⚠ same type
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/edaradd-p-arg208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown