EDAR p.Pro49=
c.147G>A · rs149582563 · VCV1165348
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.148%, mid)
Conditions
2
ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant
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 0.38 | GERP -3.2, phastCons 0.99 |
| Overall | ||
| CADD | 8.457 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.148%
Middle Eastern · 9/6,082 alleles
Filtering AF
0.0772%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0577%
Overall
0.0354%
571/1,613,848 alleles · rare
exomes 515/1,461,666 · genomes 56/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.148% | 676 |
| European (non-Finnish) | 0.0424% | 2,360 |
| Admixed American | 0.03% | 3,334 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,471 |
| South Asian | 0.0143% | 7,007 |
| African / African-American | 0.012% | 8,323 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Finnishnot grpmax-eligible | 0.00313% | 31,944 |
| East Asian | 0.00223% | 44,880 |
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.Pro49=
- Coding
- c.147G>A
- MANE Select
- NM_022336
- dbSNP
- rs149582563
- Type
- single nucleotide variant
- Location
- chr2:108930147 (GRCh38)
- Gene constraint
- LOEUF 0.927 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.01 · 1 PDB
- Residue 49
- an α-helix
Similar variants
- EDAR p.Pro49Arg Uncertain significance ★ ⚠ same residue
- EDAR p.Pro49Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- EDAR p.Pro49Gln Likely benign ★ same residue
- EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- EDAR p.Arg25Ter Pathogenic/Likely pathogenic ★★ same condition
- EDAR p.Arg358Ter Pathogenic ★★ same condition
- EDAR p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
- EDAR p.Arg89His Pathogenic/Likely pathogenic ★★ ⚠ 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-pro49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown