CD3E c.49+175G>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.77%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +175 | deep intronic (+175 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.053 | GERP -3.3 |
| Non-coding constraint | Z 1.47 | 1 kb window · o/e 0.90 · regional · uncalibrated |
| Overall | ||
| CADD | 0.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.77%
African / African-American · 737/41,578 alleles
Filtering AF
1.67%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.62%
Overall
0.515%
785/152,346 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.77% | 56 |
| Remaining individualsnot grpmax-eligible | 0.425% | 235 |
| Admixed American | 0.242% | 414 |
| European (non-Finnish) | 0.00294% | 34,020 |
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.49+175G>A
- MANE Select
- NM_000733
- dbSNP
- rs139878287
- Type
- single nucleotide variant
- Location
- chr11:118305176 (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.103+1G>A Likely pathogenic ★★ same type
- CD3E c.49+1G>C Pathogenic ★★ same type
- CD3E p.Tyr96Ter Pathogenic/Likely pathogenic ★★ same type
- CD3E c.520+5G>A Uncertain significance ★★ same type
- CD3E p.Arg192Gln Uncertain significance ★★ ⚠ same type
- CD3E p.Arg206His Uncertain significance ★★ ⚠ same type
- CD3E p.Asn25Asp Uncertain significance ★★ ⚠ same type
- CD3E p.Asn74Thr 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/cd3e-c-49-plus-175g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown