Is IL12RB1 p.Phe99= (c.297C>T) pathogenic?

IL12RB1 p.Phe99= (c.297C>T) is classified Likely benign in IL12RB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). Absent from gnomAD v4.1; Associated with Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency.

How common is IL12RB1 p.Phe99= (c.297C>T) in the general population?

IL12RB1 p.Phe99= (c.297C>T) is absent from gnomAD v4.1 (gnomAD).

IL12RB1 p.Phe99=

Q: What condition is associated with IL12RB1 p.Phe99= (c.297C>T)?

IL12RB1 p.Phe99= (c.297C>T) 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.297C>T · rs2146391015 · VCV1140731

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 4.1	GERP -0.024, phastCons 1
Overall
CADD	7.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IL12RB1
Protein: p.Phe99=
Coding: c.297C>T
MANE Select: NM_005535
dbSNP: rs2146391015
Type: single nucleotide variant
Location: chr19:18080944 (GRCh38)
Gene constraint: LOEUF 0.862 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.84 · 7 PDB
Residue 99: a β-strand; the fibronectin type-iii 1 domain

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 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
IL12RB1 p.Arg521Ter Pathogenic ★★ same condition
IL12RB1 p.Gln32Ter 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-phe99 (accessed [today's date]).

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