Is IL1A p.Ile92= (c.276C>T) pathogenic?

IL1A p.Ile92= (c.276C>T) is classified Benign in IL1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-08-24). Common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele.

IL1A p.Ile92=

Q: How common is IL1A p.Ile92= (c.276C>T) in the general population?

IL1A p.Ile92= (c.276C>T) is common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.276C>T · rs20540 · VCV775754

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele

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 1.1	GERP -2.5, phastCons 0.98
Overall
CADD	1.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.53% African / African-American · 4,896/75,016 alleles

Filtering AF 6.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.31%

Overall 0.339% 5,472/1,614,176 alleles · common exomes 2,649/1,461,878 · genomes 2,823/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.53%	15
Admixed American	0.411%	243
Remaining individualsnot grpmax-eligible	0.398%	251
Middle Eastern	0.132%	758
European (non-Finnish)	0.00576%	17,353
South Asian	0.00439%	22,771

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: IL1A
Protein: p.Ile92=
Coding: c.276C>T
MANE Select: NM_000575
dbSNP: rs20540
Type: single nucleotide variant
Location: chr2:112781647 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 74.49 · 4 PDB

Full IL1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL1A p.Asp138Asn Benign ★★ same type
IL1A p.Thr153= Likely benign ★★ same type
IL1A p.Ala238Val Uncertain significance ★ ⚠ same type
IL1A p.Ala245Asp Uncertain significance ★ ⚠ same type
IL1A p.Asn121Ser Uncertain significance ★ ⚠ same type
IL1A p.Asn141Ser Uncertain significance ★ ⚠ same type
IL1A p.Asn148Thr Uncertain significance ★ ⚠ same type
IL1A p.Asn18Lys Uncertain significance ★ ⚠ same type

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/il1a-p-ile92 (accessed [today's date]).

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