Is IL1RN p.Arg26Pro (c.77G>C) pathogenic?

IL1RN p.Arg26Pro (c.77G>C) is classified Uncertain significance in IL1RN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.1402); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with IL1RN p.Arg26Pro (c.77G>C)?

IL1RN p.Arg26Pro (c.77G>C) is associated with Inborn genetic diseases (ClinVar).

How common is IL1RN p.Arg26Pro (c.77G>C) in the general population?

IL1RN p.Arg26Pro (c.77G>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about IL1RN p.Arg26Pro (c.77G>C)?

AlphaMissense predicts likely benign (score 0.1402) — an in-silico prediction, not a clinical call.

IL1RN p.Arg26Pro

c.77G>C · rs758363942 · VCV3109284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1402 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1402	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.21	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 -0.052	GERP -0.41
Regional constraint	o/e 0.96	unconstrained · MANE · 5,243 bp · p 0.54 · regional, not allelic
Overall
CADD	9.482	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 0.0107% African / African-American · 8/74,890 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000558% 9/1,613,930 alleles · ultra-rare exomes 2/1,461,820 · genomes 7/152,110 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,361
European (non-Finnish)	8.47e-05%	1,180,011

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: IL1RN
Protein: p.Arg26Pro
Coding: c.77G>C
MANE Select: NM_173842
dbSNP: rs758363942
Type: single nucleotide variant
Location: chr2:113127701 (GRCh38)
Gene constraint: LOEUF 1.507 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 5 PDB

Full IL1RN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IL1RN p.Arg26Gln Uncertain significance ★★ ⚠ same residue
IL1RN p.Arg102Thr Uncertain significance ★★ ⚠ same condition
IL1RN p.Arg127Cys Uncertain significance ★★ ⚠ same condition
IL1RN p.Asn66Ser Uncertain significance ★★ ⚠ same condition
IL1RN p.Pro27Ser Uncertain significance ★★ ⚠ same condition
IL1RN p.Ala37Asp Uncertain significance ★ ⚠ same condition
IL1RN p.Gln119His Uncertain significance ★ ⚠ same condition
IL1RN p.Gly62Arg 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/il1rn-p-arg26pro (accessed [today's date]).

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