Is IL2RA p.Val243= (c.729G>A) pathogenic?

IL2RA p.Val243= (c.729G>A) is classified Uncertain significance in IL2RA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). Very rare (popmax 0.00297%, nfe); Associated with immunodeficiency due to CD25 deficiency.

What condition is associated with IL2RA p.Val243= (c.729G>A)?

IL2RA p.Val243= (c.729G>A) is associated with immunodeficiency due to CD25 deficiency (ClinVar).

How common is IL2RA p.Val243= (c.729G>A) in the general population?

IL2RA p.Val243= (c.729G>A) is very rare (popmax 0.00297%, nfe) (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.Val243=

c.729G>A · rs74162100 · VCV2185956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

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	Δ0.62	acceptor gain · deltas
Pangolin	Δ0.44	gain · loss 0.08 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.5	GERP 1.9, phastCons 1
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,179,804 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00223% 36/1,613,714 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,709
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Val243=
Coding: c.729G>A
MANE Select: NM_000417
dbSNP: rs74162100
Type: single nucleotide variant
Location: chr10:6018118 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.72 · 10 PDB

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.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
IL2RA p.Arg88Gln 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-val243 (accessed [today's date]).

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