EDAR p.Val284=
c.852C>T · rs754541133 · VCV2651258
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 0.78 | GERP -2.9, phastCons 0.99 |
| Overall | ||
| CADD | 4.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,058 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00376%
Overall
0.0013%
19/1,460,894 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,029 |
| South Asian | 0.00988% | 10,117 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| European (non-Finnish) | 0.000424% | 235,904 |
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.Val284=
- Coding
- c.852C>T
- MANE Select
- NM_022336
- dbSNP
- rs754541133
- Type
- single nucleotide variant
- Location
- chr2:108907971 (GRCh38)
- Gene constraint
- LOEUF 0.927 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.01 · 1 PDB
- Residue 284
- the 'disordered' region
Similar variants
- EDAR p.Val284Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- EDAR c.730+1G>T Pathogenic ★★ same type
- EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- EDAR p.Arg25Ter Pathogenic/Likely pathogenic ★★ same type
- EDAR p.Arg358Ter Pathogenic ★★ same type
- EDAR p.Arg420Gln Pathogenic/Likely pathogenic ★★ same type
- EDAR p.Arg89His Pathogenic/Likely pathogenic ★★ ⚠ same type
- EDAR p.Arg98Trp Pathogenic/Likely pathogenic ★★ 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/edar-p-val284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown