Is IGLL1 p.Ala112= (c.336C>T) pathogenic?

IGLL1 p.Ala112= (c.336C>T) is classified Likely benign in IGLL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-06). Rare (popmax 0.151%, nfe); Associated with agammaglobulinemia 2, autosomal recessive.

What condition is associated with IGLL1 p.Ala112= (c.336C>T)?

IGLL1 p.Ala112= (c.336C>T) is associated with agammaglobulinemia 2, autosomal recessive (ClinVar).

How common is IGLL1 p.Ala112= (c.336C>T) in the general population?

IGLL1 p.Ala112= (c.336C>T) is rare (popmax 0.151%, nfe) (gnomAD).

IGLL1 p.Ala112=

c.336C>T · rs140494226 · VCV538833

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.151%, nfe)

Conditions

agammaglobulinemia 2, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.4
Overall
CADD	1.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% European (non-Finnish) · 1,785/1,179,496 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.134% 2,167/1,613,226 alleles · rare exomes 1,990/1,461,208 · genomes 177/152,018 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.245%	408
European (non-Finnish)grpmax	0.151%	661
Finnishnot grpmax-eligible	0.112%	889
East Asian	0.0981%	1,020
Admixed American	0.0567%	1,765
African / African-American	0.0535%	1,869
Middle Eastern	0.0499%	2,005
South Asian	0.0362%	2,759
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,866

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala112=
Coding: c.336C>T
MANE Select: NM_020070
dbSNP: rs140494226
Type: single nucleotide variant
Location: chr22:23573572 (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 112: 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.Ala112Asp Uncertain significance ★ ⚠ same residue
IGLL1 p.Ala112Thr 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-ala112 (accessed [today's date]).

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