EDA2R p.Ser224=
c.672G>A · VCV4016146
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0691%, 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 -2.8 | GERP -1.4 |
| Overall | ||
| CADD | 0.807 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0691%
Middle Eastern · 3/4,342 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00999%
Overall
0.00173%
19/1,096,330 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0691% | 1,447 |
| Remaining individualsnot grpmax-eligible | 0.00631% | 15,860 |
| South Asian | 0.00177% | 56,355 |
| European (non-Finnish) | 0.00134% | 74,560 |
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
- EDA2R
- Protein
- p.Ser224=
- Coding
- c.672G>A
- MANE Select
- NM_021783
- Type
- single nucleotide variant
- Location
- chrX:66599706 (GRCh38)
- Structure
- AlphaFold pLDDT 69.14
Similar variants
- EDA2R p.Ser224Leu Uncertain significance ★ ⚠ same residue
- EDA2R p.Leu27= Benign ★★ same type
- EDA2R p.Pro112Ser Likely benign ★★ ⚠ same type
- EDA2R p.Tyr8His Benign ★★ same type
- EDA2R p.Ala119Val Uncertain significance ★ ⚠ same type
- EDA2R p.Arg14Gln Uncertain significance ★ ⚠ same type
- EDA2R p.Arg47Cys Uncertain significance ★ ⚠ same type
- EDA2R p.Arg95Cys Uncertain significance ★ ⚠ 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/eda2r-p-ser224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown