Is IL2RG p.Ser94= (c.282G>A) pathogenic?

IL2RG p.Ser94= (c.282G>A) is classified Benign in IL2RG (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.228%, eas); Associated with T-B+ severe combined immunodeficiency due to gamma chain deficiency.

What condition is associated with IL2RG p.Ser94= (c.282G>A)?

IL2RG p.Ser94= (c.282G>A) is associated with T-B+ severe combined immunodeficiency due to gamma chain deficiency (ClinVar).

How common is IL2RG p.Ser94= (c.282G>A) in the general population?

IL2RG p.Ser94= (c.282G>A) is rare (popmax 0.228%, eas) (gnomAD).

IL2RG p.Ser94=

Q: How is T-B+ severe combined immunodeficiency due to gamma chain deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.282G>A · rs142807857 · VCV723304

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.228%, eas)

Conditions

T-B+ severe combined immunodeficiency due to gamma chain deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP -2.9
Overall
CADD	2.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.228% East Asian · 77/33,749 alleles

Filtering AF 0.187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.0147% 177/1,205,771 alleles · rare exomes 136/1,094,446 · genomes 41/111,325 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.228%	438
African / African-American	0.111%	903
Admixed American	0.0658%	1,521
Remaining individualsnot grpmax-eligible	0.00632%	15,832
South Asian	0.00529%	18,909
European (non-Finnish)	0.000112%	891,735

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: IL2RG
Protein: p.Ser94=
Coding: c.282G>A
MANE Select: NM_000206
dbSNP: rs142807857
Type: single nucleotide variant
Location: chrX:71110676 (GRCh38)
Structure: AlphaFold pLDDT 76.75 · 14 PDB
Residue 94: a β-strand

Full IL2RG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

T-B+ severe combined immunodeficiency due to gamma chain deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For T-B+ severe combined immunodeficiency due to gamma chain deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

IL2RG p.Ser94Ter Pathogenic ★★★ same residue
IL2RG p.Ser94Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
IL2RG p.Ser94Thr Uncertain significance ★ ⚠ same residue
IL2RG c.115+1G>T Pathogenic ★★★ same condition
IL2RG c.115+2T>C Pathogenic ★★★ same condition
IL2RG c.116-1G>A Pathogenic ★★★ same condition
IL2RG c.116-2A>G Likely pathogenic ★★★ same condition
IL2RG c.269+1G>T 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/il2rg-p-ser94 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown