Is IL2RA p.Ser60= (c.180C>T) pathogenic?

IL2RA p.Ser60= (c.180C>T) is classified Conflicting classifications of pathogenicity in IL2RA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0133%, afr); Associated with immunodeficiency due to CD25 deficiency.

What condition is associated with IL2RA p.Ser60= (c.180C>T)?

IL2RA p.Ser60= (c.180C>T) is associated with immunodeficiency due to CD25 deficiency (ClinVar).

How common is IL2RA p.Ser60= (c.180C>T) in the general population?

IL2RA p.Ser60= (c.180C>T) is ultra-rare (popmax 0.0133%, afr) (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.Ser60=

c.180C>T · rs74162093 · VCV953264

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Conditions

immunodeficiency due to CD25 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Constraint at this position
Conservation	phyloP -9.2	GERP -3.5
Overall
CADD	3.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,912 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.0044% 71/1,614,022 alleles · ultra-rare exomes 61/1,461,868 · genomes 10/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,491
European (non-Finnish)	0.00483%	20,702
Remaining individualsnot grpmax-eligible	0.0032%	31,245
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,082

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.Ser60=
Coding: c.180C>T
MANE Select: NM_000417
dbSNP: rs74162093
Type: single nucleotide variant
Location: chr10:6025910 (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 60: 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.Ser60Ile 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-ser60 (accessed [today's date]).

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