Is IL10RA p.Pro428= (c.1284G>A) pathogenic?

IL10RA p.Pro428= (c.1284G>A) is classified Likely benign in IL10RA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Very rare (popmax 0.00669%, eas); Associated with inflammatory bowel disease 28.

What condition is associated with IL10RA p.Pro428= (c.1284G>A)?

IL10RA p.Pro428= (c.1284G>A) is associated with inflammatory bowel disease 28 (ClinVar).

How common is IL10RA p.Pro428= (c.1284G>A) in the general population?

IL10RA p.Pro428= (c.1284G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

IL10RA p.Pro428=

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.1284G>A · rs543841858 · VCV1111618

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

inflammatory bowel disease 28

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 -0.28	GERP -4
Overall
CADD	1.411	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,874 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00229% 37/1,614,222 alleles · very rare exomes 34/1,461,872 · genomes 3/152,350 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,958
South Asian	0.00439%	22,772
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.00212%	47,201
Admixed American	0.00167%	60,034
African / African-American	0.00133%	75,064

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.Pro428=
Coding: c.1284G>A
MANE Select: NM_001558
dbSNP: rs543841858
Type: single nucleotide variant
Location: chr11:117999188 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 63.05 · 7 PDB
Residue 428: the 'disordered' region

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.Pro428Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro428 (accessed [today's date]).

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