Is IL2RA p.Ser84= (c.252C>T) pathogenic?

IL2RA p.Ser84= (c.252C>T) is classified Conflicting classifications of pathogenicity in IL2RA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-06). Very rare (popmax 0.005%, amr); Associated with immunodeficiency due to CD25 deficiency.

What condition is associated with IL2RA p.Ser84= (c.252C>T)?

IL2RA p.Ser84= (c.252C>T) is associated with immunodeficiency due to CD25 deficiency (ClinVar).

How common is IL2RA p.Ser84= (c.252C>T) in the general population?

IL2RA p.Ser84= (c.252C>T) is very rare (popmax 0.005%, amr) (gnomAD).

How is Immunodeficiency due to CD25 deficiency inherited?

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

IL2RA p.Ser84=

c.252C>T · rs1034684102 · VCV879205

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

immunodeficiency due to CD25 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.7	GERP -2.8
Overall
CADD	1.314	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000372% 6/1,613,946 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
East Asian	0.00445%	22,449
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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: IL2RA
Protein: p.Ser84=
Coding: c.252C>T
MANE Select: NM_000417
dbSNP: rs1034684102
Type: single nucleotide variant
Location: chr10:6025838 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.72 · 10 PDB
Residue 84: a disulfide bond; a β-strand; the sushi 1 domain

Full IL2RA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency due to CD25 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to CD25 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

IL2RA p.Ser84Thr Uncertain significance ★ ⚠ same residue
IL2RA p.Gln101Ter Pathogenic ★★ same condition
IL2RA c.655+4C>T Uncertain significance ★★ same condition
IL2RA c.*1026G>T Uncertain significance ★★ same condition
IL2RA p.Arg206Cys Uncertain significance ★★ ⚠ same condition
IL2RA p.Arg206His Uncertain significance ★★ ⚠ same condition
IL2RA p.Arg263Trp Uncertain significance ★★ ⚠ same condition
IL2RA p.Arg56His Uncertain significance ★★ ⚠ 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/il2ra-p-ser84 (accessed [today's date]).

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