Is IL10RB p.Pro23= (c.69T>C) pathogenic?

IL10RB p.Pro23= (c.69T>C) is classified Likely benign in IL10RB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). Very rare (popmax 8.48e-05%, nfe); Associated with inflammatory bowel disease 25.

What condition is associated with IL10RB p.Pro23= (c.69T>C)?

IL10RB p.Pro23= (c.69T>C) is associated with inflammatory bowel disease 25 (ClinVar).

How common is IL10RB p.Pro23= (c.69T>C) in the general population?

IL10RB p.Pro23= (c.69T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

IL10RB p.Pro23=

Q: How is Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome inherited?

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

c.69T>C · VCV3659727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

inflammatory bowel disease 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.003	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 2.5, phastCons 1
Overall
CADD	9.871	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,728 alleles

Overall 6.2e-05% 1/1,613,896 alleles · very rare exomes 1/1,461,538 · genomes 0/152,358 · joint denominator

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: IL10RB
Protein: p.Pro23=
Coding: c.69T>C
MANE Select: NM_000628
Type: single nucleotide variant
Location: chr21:33268413 (GRCh38)
Gene constraint: LOEUF 1.053 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 5 PDB
Residue 23: an α-helix; the fibronectin type-iii 1 domain

Full IL10RB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inflammatory bowel disease 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

IL10RB p.Arg130His Uncertain significance ★★ ⚠ same condition
IL10RB p.Asp110Asn Uncertain significance ★★ ⚠ same condition
IL10RB p.Glu141Lys Uncertain significance ★★ ⚠ same condition
IL10RB p.Gly10Ala Uncertain significance ★★ ⚠ same condition
IL10RB p.Ser286Leu Uncertain significance ★★ ⚠ same condition
IL10RB p.Ser304Asn Uncertain significance ★★ ⚠ same condition
IL10RB p.Thr217Met Uncertain significance ★★ ⚠ same condition
IL10RB p.Tyr149Cys 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/il10rb-p-pro23 (accessed [today's date]).

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