IGF2 p.Pro109=
c.327C>T · VCV3627393
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00723%, sas)
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 4.5 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 14.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00723%
South Asian · 6/82,996 alleles
Filtering AF
0.00309%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00231%
36/1,556,562 alleles · very rare
exomes 32/1,404,368 · genomes 4/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00723% | 13,833 |
| European (non-Finnish) | 0.00235% | 42,564 |
| Admixed American | 0.0019% | 52,704 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,860 |
| African / African-American | 0.00136% | 73,278 |
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.Pro109=
- Coding
- c.327C>T
- MANE Select
- NM_000612
- Type
- single nucleotide variant
- Location
- chr11:2133203 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
- Residue 109
- a UniProt-annotated variant site (in srs3)
Similar variants
- INS-IGF2 p.Arg109Gly 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-pro109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown