EDAR p.Thr8=
c.24G>A · VCV4956426
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -4.5 |
| Overall | ||
| CADD | 1.816 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,944 alleles
Filtering AF
0.00138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00116%
Overall
0.00173%
28/1,613,870 alleles · very rare
exomes 26/1,461,674 · genomes 2/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,981 |
| East Asian | 0.00223% | 44,876 |
| European (non-Finnish) | 0.00203% | 49,168 |
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.Thr8=
- Coding
- c.24G>A
- MANE Select
- NM_022336
- Type
- single nucleotide variant
- Location
- chr2:108930991 (GRCh38)
- Gene constraint
- LOEUF 0.927 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.01 · 1 PDB
Similar variants
- EDAR p.Thr8Met Uncertain significance ★ ⚠ 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-thr8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown