Is IL10RA p.Pro3Arg (c.8C>G) pathogenic?

IL10RA p.Pro3Arg (c.8C>G) is classified Uncertain significance in IL10RA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0787); Ultra-rare (popmax 0.0178%, sas); Associated with inflammatory bowel disease 28.

What condition is associated with IL10RA p.Pro3Arg (c.8C>G)?

IL10RA p.Pro3Arg (c.8C>G) is associated with inflammatory bowel disease 28 (ClinVar).

How common is IL10RA p.Pro3Arg (c.8C>G) in the general population?

IL10RA p.Pro3Arg (c.8C>G) is ultra-rare (popmax 0.0178%, sas) (gnomAD).

What do computational predictors say about IL10RA p.Pro3Arg (c.8C>G)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

IL10RA p.Pro3Arg

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.8C>G · rs56008037 · VCV947503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inflammatory bowel disease 28

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -3.03	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 -2.7	GERP -3
Regional constraint	o/e 0.88	unconstrained · MANE · 13 kb · p 0.002 · regional, not allelic
Overall
CADD	0.887	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

Grpmax group 0.0178% South Asian · 15/84,320 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00883%

Overall 0.00154% 24/1,555,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0178%	5,621
Admixed American	0.00385%	25,957
Remaining individualsnot grpmax-eligible	0.00166%	60,182
European (non-Finnish)	0.000522%	191,577

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: IL10RA
Protein: p.Pro3Arg
Coding: c.8C>G
MANE Select: NM_001558
dbSNP: rs56008037
Type: single nucleotide variant
Location: chr11:117986475 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 63.05 · 7 PDB

Full IL10RA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inflammatory bowel disease 28 — 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

IL10RA p.Pro3Gln Likely benign ★★ same residue
IL10RA c.68-1G>A Likely pathogenic ★★ same condition
IL10RA p.Arg101Trp Pathogenic/Likely pathogenic ★★ same condition
IL10RA p.Arg117Cys Pathogenic ★★ same condition
IL10RA p.Arg165Ter Pathogenic/Likely pathogenic ★★ same condition
IL10RA p.Arg212Ter Pathogenic ★★ same condition
IL10RA p.Thr179= Pathogenic/Likely pathogenic ★★ same condition
IL10RA c.188+3G>A 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/il10ra-p-pro3arg (accessed [today's date]).

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