Is IGLL1 p.Pro18= (c.54C>G) pathogenic?

IGLL1 p.Pro18= (c.54C>G) is classified Likely benign in IGLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). Very rare (popmax 0.00192%, amr); Associated with agammaglobulinemia 2, autosomal recessive.

What condition is associated with IGLL1 p.Pro18= (c.54C>G)?

IGLL1 p.Pro18= (c.54C>G) is associated with agammaglobulinemia 2, autosomal recessive (ClinVar).

How common is IGLL1 p.Pro18= (c.54C>G) in the general population?

IGLL1 p.Pro18= (c.54C>G) is very rare (popmax 0.00192%, amr) (gnomAD).

IGLL1 p.Pro18=

c.54C>G · rs1437649021 · VCV799531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00192%, amr)

Conditions

agammaglobulinemia 2, autosomal recessive

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 -1.5	GERP -3
Overall
CADD	1.434	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00192% Admixed American · 1/52,100 alleles

Overall 6.42e-05% 1/1,558,840 alleles · very rare exomes 1/1,406,526 · genomes 0/152,314 · joint denominator

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: IGLL1
Protein: p.Pro18=
Coding: c.54C>G
MANE Select: NM_020070
dbSNP: rs1437649021
Type: single nucleotide variant
Location: chr22:23580137 (GRCh38)
Gene constraint: LOEUF 1.844 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 3 PDB

Full IGLL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

agammaglobulinemia 2, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IGLL1 p.Pro18Leu Uncertain significance ★★ ⚠ same residue
IGLL1 p.Pro18Ser Uncertain significance ★ ⚠ same residue
IGLL1 p.Ala12Val Uncertain significance ★★ ⚠ same condition
IGLL1 p.Ala174Ser Uncertain significance ★★ ⚠ same condition
IGLL1 p.Arg23His Uncertain significance ★★ ⚠ same condition
IGLL1 p.Arg2Lys Uncertain significance ★★ ⚠ same condition
IGLL1 p.Arg40Cys Uncertain significance ★★ ⚠ same condition
IGLL1 p.Arg48Gly 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/igll1-p-pro18 (accessed [today's date]).

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