Is IL2RA p.Pro28= (c.84G>A) pathogenic?

IL2RA p.Pro28= (c.84G>A) is classified Benign in IL2RA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 20.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency due to CD25 deficiency.

What condition is associated with IL2RA p.Pro28= (c.84G>A)?

IL2RA p.Pro28= (c.84G>A) is associated with immunodeficiency due to CD25 deficiency (ClinVar).

How is Immunodeficiency due to CD25 deficiency inherited?

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

IL2RA p.Pro28=

Q: How common is IL2RA p.Pro28= (c.84G>A) in the general population?

IL2RA p.Pro28= (c.84G>A) is common (popmax 20.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.84G>A · rs2228150 · VCV300261

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 20.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency due to CD25 deficiency

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 -8.7	GERP -3.5
Overall
CADD	0.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.6% African / African-American · 15,420/74,918 alleles

Filtering AF 20.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.2%

Overall 3.82% 61,639/1,613,062 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	20.6%	5
Amishnot grpmax-eligible	8.68%	12
South Asian	6.72%	15
Middle Eastern	5.41%	18
Remaining individualsnot grpmax-eligible	4.24%	24
Admixed American	3.51%	29
Ashkenazi Jewishnot grpmax-eligible	3.33%	30
European (non-Finnish)	2.8%	36
Finnishnot grpmax-eligible	1.41%	71
East Asian	0.105%	955

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.Pro28=
Coding: c.84G>A
MANE Select: NM_000417
dbSNP: rs2228150
Type: single nucleotide variant
Location: chr10:6026006 (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 28: a disulfide bond; an α-helix; 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.Pro28Leu 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-pro28 (accessed [today's date]).

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