Is IL7R p.Ala33= (c.99A>G) pathogenic?

IL7R p.Ala33= (c.99A>G) is classified Likely benign in IL7R (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-26). Very rare (popmax 0.000254%, nfe); Associated with immunodeficiency 104.

What condition is associated with IL7R p.Ala33= (c.99A>G)?

IL7R p.Ala33= (c.99A>G) is associated with immunodeficiency 104 (ClinVar).

How common is IL7R p.Ala33= (c.99A>G) in the general population?

IL7R p.Ala33= (c.99A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

IL7R p.Ala33=

c.99A>G · rs992083666 · VCV2824349

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

immunodeficiency 104

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 -2.7	GERP -4.4
Overall
CADD	2.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,596 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,330 alleles · very rare

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: IL7R
Protein: p.Ala33=
Coding: c.99A>G
MANE Select: NM_002185
dbSNP: rs992083666
Type: single nucleotide variant
Location: chr5:35860868 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52 · 8 PDB

Full IL7R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 104 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IL7R c.221+1G>A Pathogenic ★★★ same condition
IL7R c.221+2T>G Pathogenic ★★★ same condition
IL7R c.537+1G>A Pathogenic ★★★ same condition
IL7R c.538-1G>A Pathogenic ★★★ same condition
IL7R c.83-2A>T Pathogenic ★★★ same condition
IL7R p.Arg206Ter Pathogenic ★★★ same condition
IL7R p.Cys118Tyr Pathogenic ★★★ same condition
IL7R p.Gln89Ter Likely 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/il7r-p-ala33 (accessed [today's date]).

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