Is IGLL1 p.Ser100= (c.300C>T) pathogenic?

IGLL1 p.Ser100= (c.300C>T) is classified Benign in IGLL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with agammaglobulinemia 2, autosomal recessive.

What condition is associated with IGLL1 p.Ser100= (c.300C>T)?

IGLL1 p.Ser100= (c.300C>T) is associated with agammaglobulinemia 2, autosomal recessive (ClinVar).

IGLL1 p.Ser100=

Q: How common is IGLL1 p.Ser100= (c.300C>T) in the general population?

IGLL1 p.Ser100= (c.300C>T) is common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.300C>T · rs115303391 · VCV471477

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele

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 -15	GERP -3.1
Overall
CADD	1.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.9% African / African-American · 8,886/74,904 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.6%

Overall 0.673% 10,853/1,613,186 alleles · common exomes 5,652/1,460,972 · genomes 5,201/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.9%	8
Ashkenazi Jewishnot grpmax-eligible	0.933%	107
Remaining individualsnot grpmax-eligible	0.869%	115
Admixed American	0.816%	123
Middle Eastern	0.462%	216
European (non-Finnish)	0.0522%	1,917
South Asian	0.0154%	6,505
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.Ser100=
Coding: c.300C>T
MANE Select: NM_020070
dbSNP: rs115303391
Type: single nucleotide variant
Location: chr22:23574989 (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 100: the 'j 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.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
IGLL1 p.Arg60Gln Uncertain significance ★★ ⚠ same condition
IGLL1 p.Arg60Gly 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-ser100 (accessed [today's date]).

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