Is IL7R p.Pro197fs (c.589_598del) pathogenic?

IL7R p.Pro197fs (c.589598del) is classified Pathogenic in IL7R (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). Very rare (popmax 0.000678%, nfe); Associated with immunodeficiency 104.

What condition is associated with IL7R p.Pro197fs (c.589_598del)?

IL7R p.Pro197fs (c.589_598del) is associated with immunodeficiency 104 (ClinVar).

How common is IL7R p.Pro197fs (c.589_598del) in the general population?

IL7R p.Pro197fs (c.589_598del) is very rare (popmax 0.000678%, nfe) (gnomAD).

IL7R p.Pro197fs

c.589_598del · rs1471668405 · VCV2734715

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

immunodeficiency 104

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.3	GERP -4.7
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,924 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,910 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.Pro197fs
Coding: c.589_598del
MANE Select: NM_002185
dbSNP: rs1471668405
Type: Deletion
Location: chr5:35873528 (GRCh38)
Gene constraint: LOEUF 0.981 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.52 · 8 PDB
Residue 197: the fibronectin type-iii domain

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 p.Pro197= Likely benign ★★ same residue
IL7R p.Pro197Gln Uncertain significance ★ ⚠ same residue
IL7R p.Pro197Leu Uncertain significance ★ ⚠ same residue
IL7R p.Phe146fs Pathogenic/Likely pathogenic ★★ same condition
IL7R p.Ala76fs Pathogenic ★ same condition
IL7R p.Asn27fs Pathogenic ★ same condition
IL7R p.Cys287fs Pathogenic ★ same condition
IL7R p.Glu172fs 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-pro197fs (accessed [today's date]).

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