Is IGLL1 p.Pro16Ser (c.46C>T) pathogenic?

IGLL1 p.Pro16Ser (c.46C>T) is classified Uncertain significance in IGLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). AlphaMissense: likely benign (0.0836); No allele count reported in gnomAD v4.1 (AN 1,554,780); Associated with agammaglobulinemia 2, autosomal recessive.

What condition is associated with IGLL1 p.Pro16Ser (c.46C>T)?

IGLL1 p.Pro16Ser (c.46C>T) is associated with agammaglobulinemia 2, autosomal recessive (ClinVar).

How common is IGLL1 p.Pro16Ser (c.46C>T) in the general population?

IGLL1 p.Pro16Ser (c.46C>T) is no allele count reported in gnomAD v4.1 (AN 1,554,780) (gnomAD).

What do computational predictors say about IGLL1 p.Pro16Ser (c.46C>T)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

IGLL1 p.Pro16Ser

c.46C>T · rs1298398827 · VCV2733911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,554,780)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 2, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP -2.3
Regional constraint	o/e 1.02	unconstrained · MANE · 6,921 bp · p 0.75 · regional, not allelic
Overall
CADD	9.075	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,554,780). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: IGLL1
Protein: p.Pro16Ser
Coding: c.46C>T
MANE Select: NM_020070
dbSNP: rs1298398827
Type: single nucleotide variant
Location: chr22:23580145 (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.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-pro16ser (accessed [today's date]).

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