Is IGLL1 p.Pro120= (c.360G>A) pathogenic?

IGLL1 p.Pro120= (c.360G>A) is classified Likely benign in IGLL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-23). Rare (popmax 0.149%, mid); Associated with agammaglobulinemia 2, autosomal recessive.

What condition is associated with IGLL1 p.Pro120= (c.360G>A)?

IGLL1 p.Pro120= (c.360G>A) is associated with agammaglobulinemia 2, autosomal recessive (ClinVar).

How common is IGLL1 p.Pro120= (c.360G>A) in the general population?

IGLL1 p.Pro120= (c.360G>A) is rare (popmax 0.149%, mid) (gnomAD).

IGLL1 p.Pro120=

c.360G>A · rs184173813 · VCV747278

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Conditions

agammaglobulinemia 2, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.085	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.4
Overall
CADD	4.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% Middle Eastern · 9/6,022 alleles

Filtering AF 0.078% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0582%

Overall 0.00613% 99/1,613,810 alleles · rare exomes 91/1,461,600 · genomes 8/152,210 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	669
South Asian	0.034%	2,937
Finnishnot grpmax-eligible	0.0219%	4,573
Remaining individualsnot grpmax-eligible	0.016%	6,249
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,799
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,499
European (non-Finnish)	0.00237%	42,137
East Asian	0.00223%	44,876

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.Pro120=
Coding: c.360G>A
MANE Select: NM_020070
dbSNP: rs184173813
Type: single nucleotide variant
Location: chr22:23573548 (GRCh38)
Gene constraint: LOEUF 1.844 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 3 PDB
Residue 120: an α-helix; the ig-like c1-type domain; the 'c region' region

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.Pro120Gln Uncertain significance ★ ⚠ same residue
IGLL1 p.Pro120Leu Likely benign ★ ⚠ 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-pro120 (accessed [today's date]).

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