IGF2 p.Ser74Thr
c.221G>C · VCV3360772
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2166 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2166 | likely benign |
|---|---|---|
| REVEL | 0.692 | pathogenic-leaning |
| SaProt | LLR -8.51 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor loss, 1 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.3 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.38 | unconstrained · MANE · 1,851 bp · p 3.2e-08 · regional, not allelic |
| Overall | ||
| CADD | 24.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- IGF2
- Protein
- p.Ser74Thr
- Coding
- c.221G>C
- MANE Select
- NM_000612
- Type
- single nucleotide variant
- Location
- chr11:2133602 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
- Residue 74
- a UniProt-annotated variant site (in srs3); the 'a' region
Similar variants
- IGF2 c.157+5G>A Pathogenic ★★ same type
- IGF2 p.Glu36Ter Pathogenic/Likely pathogenic ★★ same type
- IGF2 p.Gly34Cys Likely pathogenic ★★ same type
- IGF2 p.Ser20Ter Likely pathogenic ★★ same type
- IGF2 p.Ala167Ser Uncertain significance ★★ ⚠ same type
- IGF2 p.Arg138Trp Uncertain significance ★★ ⚠ same type
- IGF2 p.Arg154Cys Uncertain significance ★★ ⚠ same type
- IGF2 p.Arg156Cys 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/igf2-p-ser74thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown