Is IL2RG p.Val67= (c.201C>T) pathogenic?

IL2RG p.Val67= (c.201C>T) is classified Benign/Likely benign in IL2RG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0229%, mid); Associated with T-B+ severe combined immunodeficiency due to gamma chain deficiency.

How common is IL2RG p.Val67= (c.201C>T) in the general population?

IL2RG p.Val67= (c.201C>T) is ultra-rare (popmax 0.0229%, mid) (gnomAD).

IL2RG p.Val67=

Q: What condition is associated with IL2RG p.Val67= (c.201C>T)?

IL2RG p.Val67= (c.201C>T) is associated with T-B+ severe combined immunodeficiency due to gamma chain deficiency, combined immunodeficiency, X-linked (ClinVar).

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.201C>T · rs756100347 · VCV795771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, mid)

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 -3.8	GERP -3.8
Overall
CADD	2.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0229% Middle Eastern · 1/4,366 alleles

Filtering AF 0.00236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00265% 32/1,206,102 alleles · ultra-rare exomes 30/1,094,801 · genomes 2/111,301 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0229%	4,366
South Asian	0.0071%	14,088
Admixed American	0.00439%	22,779
Remaining individualsnot grpmax-eligible	0.00421%	23,739
European (non-Finnish)	0.00258%	38,812

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.Val67=
Coding: c.201C>T
MANE Select: NM_000206
dbSNP: rs756100347
Type: single nucleotide variant
Location: chrX:71110965 (GRCh38)
Structure: AlphaFold pLDDT 76.75 · 14 PDB
Residue 67: a turn

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

Also linked: combined immunodeficiency, X-linked

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 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
IL2RG c.455-2A>C Pathogenic ★★★ same condition
IL2RG c.455-2A>T Pathogenic ★★★ same condition
IL2RG c.924+1G>A 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-val67 (accessed [today's date]).

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