EDA p.Trp274Ter
c.822G>A · rs397516675 · VCV163321
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
EDA-related disorder
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 in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 8 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 4.8, phastCons 1 |
| Overall | ||
| CADD | 40.0 | 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
- EDA
- Protein
- p.Trp274Ter
- Coding
- c.822G>A
- MANE Select
- NM_001399
- dbSNP
- rs397516675
- Type
- single nucleotide variant
- Location
- chrX:70033426 (GRCh38)
- Structure
- AlphaFold pLDDT 70.59 · 3 PDB
- Residue 274
- the thd domain; a UniProt-annotated variant site (in xhed)
Similar variants
- EDA p.Trp274Arg Likely pathogenic ★ same residue
- EDA p.Trp274Cys Likely pathogenic ★ same residue
- EDA p.Trp274fs Pathogenic ★★ same residue
- EDA c.526+2T>C Pathogenic/Likely pathogenic ★★ same condition
- EDA c.526+5G>T Likely pathogenic ★★ same condition
- EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same condition
- EDA c.706+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EDA c.707-13T>G 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/eda-p-trp274ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown