CD3E c.70+4del
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00213%, nfe)
Conditions
1
severe combined immunodeficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -1.2, phastCons 0.012 |
| Non-coding constraint | Z 0.47 | 1 kb window · o/e 0.97 · regional · uncalibrated |
| Overall | ||
| CADD | 14.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00213%
European (non-Finnish) · 25/1,173,752 alleles
Filtering AF
0.00146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00162%
26/1,604,888 alleles · very rare
exomes 24/1,452,780 · genomes 2/152,108 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00213% | 46,950 |
| South Asian | 0.0011% | 90,742 |
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
- CD3E
- Coding
- c.70+4del
- MANE Select
- NM_000733
- dbSNP
- rs193922619
- Type
- Deletion
- Location
- chr11:118307312 (GRCh38)
- Gene constraint
- LOEUF 0.659 · pLI 0.47 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.56 · 44 PDB
Similar variants
- CD3E c.567+65_567+66del Uncertain significance ★ same condition
- CD3E p.Tyr96Ter Pathogenic/Likely pathogenic ★★ same condition
- CD3E p.Leu58fs Pathogenic ★★ same type
- CD3E p.Gly143fs Pathogenic ★ same type
- CD3E p.Ser88fs Pathogenic ★ same type
- CD3E p.Gly68_Gly76del Uncertain significance ★ same type
- CD3E p.Lys177fs Uncertain significance ★ same type
- CD3E c.353-5del Benign ★ 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/cd3e-c-70-plus-4del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown