IGF2 p.Pro102=
c.306G>A · rs536204564 · VCV1977706
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00335%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.45 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.40 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.5 | GERP 0.81, phastCons 1 |
| Overall | ||
| CADD | 23.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00335%
Admixed American · 2/59,638 alleles
Filtering AF
0.000556%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000621%
10/1,610,276 alleles · very rare
exomes 9/1,457,976 · genomes 1/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00335% | 29,819 |
| European (non-Finnish) | 0.000679% | 147,317 |
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
- IGF2
- Protein
- p.Pro102=
- Coding
- c.306G>A
- MANE Select
- NM_000612
- dbSNP
- rs536204564
- Type
- single nucleotide variant
- Location
- chr11:2133517 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
- Residue 102
- a UniProt-annotated variant site (in srs3)
Similar variants
- IGF2 p.Pro102Leu Uncertain significance ★★ ⚠ same residue
- 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
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-pro102 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown