IL7R p.Ser44=
c.132C>T · rs11567704 · VCV377976
ClinGen expert panel — Severe Combined Immunodeficiency Disease VCEP
Likely Benign for severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive. Applied ACMG criteria (verbatim):
BS1 BP7
Curation rationale (ClinGen, verbatim)
The c.132C>T (p.Ser44=) variant (NM_002185.5) variant in IL7R is a synonymous (silent) variant that is not predicted to impact splicing (BP7). The filtering allele frequency (the lower threshold of the 95% CI of 342/24962) of the c.132C>T variant in IL7R is 0.01271 in exomes and 0.01082 in genomes for African/African American chromosomes by gnomAD v2.1.1. Both values are higher than the ClinGen SCID VCEP threshold (0.00126) for BS1 and therefore meet this criterion (BS1). In summary, this variant meets the criteria to be classified as likely benign for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BP7 and BS1. (VCEP specifications version 1).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 0.11 | GERP 0.49, phastCons 0.98 |
| Overall | ||
| CADD | 8.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.39% | 72 |
| Middle Eastern | 0.314% | 319 |
| Admixed American | 0.153% | 652 |
| Remaining individualsnot grpmax-eligible | 0.118% | 844 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0237% | 4,225 |
| European (non-Finnish) | 0.00492% | 20,335 |
| South Asian | 0.00329% | 30,356 |
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
- IL7R
- Protein
- p.Ser44=
- Coding
- c.132C>T
- MANE Select
- NM_002185
- dbSNP
- rs11567704
- Type
- single nucleotide variant
- Location
- chr5:35860901 (GRCh38)
- Gene constraint
- LOEUF 0.981 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.52 · 8 PDB
- Residue 44
- a disulfide bond; a β-strand
Similar variants
- IL7R p.Ser44Arg Uncertain significance ★ ⚠ same residue
- IL7R c.221+1G>A Pathogenic ★★★ same condition
- IL7R c.221+2T>G Pathogenic ★★★ same condition
- IL7R c.537+1G>A Pathogenic ★★★ same condition
- IL7R c.538-1G>A Pathogenic ★★★ same condition
- IL7R c.83-2A>T Pathogenic ★★★ same condition
- IL7R p.Arg206Ter Pathogenic ★★★ same condition
- IL7R p.Cys118Tyr 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/il7r-p-ser44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown