EDAR p.Cys428Ter
c.1284T>A · rs886041005 · VCV267731
Likely pathogenic
No assertion criteria
Classification
Likely pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
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. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.47 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP -3.6 |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EDAR
- Protein
- p.Cys428Ter
- Coding
- c.1284T>A
- MANE Select
- NM_022336
- dbSNP
- rs886041005
- Type
- single nucleotide variant
- Location
- chr2:108896970 (GRCh38)
- Gene constraint
- LOEUF 0.927 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.01 · 1 PDB
- Residue 428
- the death domain
Similar variants
- EDAR p.Cys428Arg Pathogenic/Likely pathogenic ★★ same residue
- EDAR p.Cys428Trp Conflicting classifications of pathogenicity ★ ⚠ 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
- EDAR p.Arg98Trp 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-cys428ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown