Is IL7R p.Pro197= (c.591G>A) pathogenic?

IL7R p.Pro197= (c.591G>A) is classified Likely benign in IL7R (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-16). Very rare (popmax 0.00533%, afr); Associated with immunodeficiency 104.

What condition is associated with IL7R p.Pro197= (c.591G>A)?

IL7R p.Pro197= (c.591G>A) is associated with immunodeficiency 104 (ClinVar).

How common is IL7R p.Pro197= (c.591G>A) in the general population?

IL7R p.Pro197= (c.591G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

IL7R p.Pro197=

c.591G>A · rs201431556 · VCV2728177

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

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 -2.3	GERP -2.1
Overall
CADD	1.463	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,010 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00204% 33/1,613,926 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,753
European (non-Finnish)	0.00237%	42,138
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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.Pro197=
Coding: c.591G>A
MANE Select: NM_002185
dbSNP: rs201431556
Type: single nucleotide variant
Location: chr5:35873533 (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.Pro197Gln Uncertain significance ★ ⚠ same residue
IL7R p.Pro197Leu Uncertain significance ★ ⚠ same residue
IL7R p.Pro197fs Pathogenic ★ same residue
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

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-pro197 (accessed [today's date]).

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