IL21 p.Ser74=
c.222A>G · rs141088343 · VCV1080706
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.85 | GERP 0.41, phastCons 0.012 |
| Overall | ||
| CADD | 9.559 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,178,454 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00031%
5/1,610,982 alleles · very rare
exomes 4/1,458,726 · genomes 1/152,256 · 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
- IL21
- Protein
- p.Ser74=
- Coding
- c.222A>G
- MANE Select
- NM_021803
- dbSNP
- rs141088343
- Type
- single nucleotide variant
- Location
- chr4:122615820 (GRCh38)
- Gene constraint
- LOEUF 0.45 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 83.92 · 3 PDB
- Residue 74
- an α-helix
Similar variants
- IL21 p.Arg40His Uncertain significance ★★ ⚠ same type
- IL21 p.Glu93Lys Uncertain significance ★★ ⚠ same type
- IL21 p.Gly113Arg Uncertain significance ★★ ⚠ same type
- IL21 p.Ile18Val Uncertain significance ★★ ⚠ same type
- IL21 p.Lys106Arg Uncertain significance ★★ ⚠ same type
- IL21 p.Met16Thr Uncertain significance ★★ ⚠ same type
- IL21 p.Pro132Thr Uncertain significance ★★ ⚠ same type
- IL21 p.Ser28Asn 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/il21-p-ser74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown