Is IGLL1 p.Val196= (c.588C>T) pathogenic?

IGLL1 p.Val196= (c.588C>T) is classified Likely benign in IGLL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.087%, eas); Associated with agammaglobulinemia 2, autosomal recessive.

What condition is associated with IGLL1 p.Val196= (c.588C>T)?

IGLL1 p.Val196= (c.588C>T) is associated with agammaglobulinemia 2, autosomal recessive (ClinVar).

How common is IGLL1 p.Val196= (c.588C>T) in the general population?

IGLL1 p.Val196= (c.588C>T) is ultra-rare (popmax 0.087%, eas) (gnomAD).

IGLL1 p.Val196=

c.588C>T · rs151337964 · VCV1146425

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.087%, eas)

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 2	GERP 1.7, phastCons 1
Overall
CADD	0.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.087% East Asian · 39/44,846 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.0262% 423/1,613,960 alleles · ultra-rare exomes 369/1,461,764 · genomes 54/152,196 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.087%	1,150
Admixed American	0.05%	2,001
European (non-Finnish)	0.0257%	3,894
Remaining individualsnot grpmax-eligible	0.024%	4,166
South Asian	0.0231%	4,337
Middle Eastern	0.0165%	6,060
African / African-American	0.012%	8,335
Finnishnot grpmax-eligible	0.00625%	16,007
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Val196=
Coding: c.588C>T
MANE Select: NM_020070
dbSNP: rs151337964
Type: single nucleotide variant
Location: chr22:23573320 (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 196: the ig-like c1-type domain; a β-strand; 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.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-val196 (accessed [today's date]).

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