Is IL12RB1 p.Pro3= (c.9G>A) pathogenic?

IL12RB1 p.Pro3= (c.9G>A) is classified Likely benign in IL12RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-09). Very rare (popmax 0.000763%, nfe); Associated with Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency.

How common is IL12RB1 p.Pro3= (c.9G>A) in the general population?

IL12RB1 p.Pro3= (c.9G>A) is very rare (popmax 0.000763%, nfe) (gnomAD).

IL12RB1 p.Pro3=

Q: What condition is associated with IL12RB1 p.Pro3= (c.9G>A)?

IL12RB1 p.Pro3= (c.9G>A) is associated with Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (ClinVar).

Q: How is Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.9G>A · rs1393654635 · VCV1904411

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

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 -0.12	GERP 0.008
Overall
CADD	6.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,178,968 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000807% 13/1,610,718 alleles · very rare exomes 9/1,458,624 · genomes 4/152,094 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00642%	15,586
European (non-Finnish)grpmax	0.000763%	130,997

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: IL12RB1
Protein: p.Pro3=
Coding: c.9G>A
MANE Select: NM_005535
dbSNP: rs1393654635
Type: single nucleotide variant
Location: chr19:18086815 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.84 · 7 PDB
Residue 3: a UniProt-annotated variant site (in)

Full IL12RB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

IL12RB1 p.Pro3Leu Uncertain significance ★★ ⚠ same residue
IL12RB1 p.Pro3Gln Uncertain significance ★ ⚠ same residue
IL12RB1 c.1791+2T>G Pathogenic ★★ same condition
IL12RB1 c.64+2T>G Pathogenic ★★ same condition
IL12RB1 p.Arg173Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
IL12RB1 p.Arg211Pro Pathogenic ★★ same condition
IL12RB1 p.Arg283Ter Pathogenic ★★ same condition
IL12RB1 p.Arg486Ter Pathogenic ★★ 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/il12rb1-p-pro3 (accessed [today's date]).

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