IGF2 p.Pro173=
c.519A>C · VCV3388610
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000262%, nfe)
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 -1.9 | GERP -1.4 |
| Overall | ||
| CADD | 2.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000262%
European (non-Finnish) · 3/1,146,162 alleles
Filtering AF
7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000194%
3/1,545,982 alleles · very rare
exomes 3/1,394,160 · genomes 0/151,822 · 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
- IGF2
- Protein
- p.Pro173=
- Coding
- c.519A>C
- MANE Select
- NM_000612
- Type
- single nucleotide variant
- Location
- chr11:2133011 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
- Residue 173
- a UniProt-annotated variant site (in srs3); a UniProt-annotated variant site (in); the 'disordered' region
Similar variants
- IGF2 p.Pro173Gln Uncertain significance ★★ ⚠ same residue
- IGF2 p.Pro173Arg Uncertain significance ★ ⚠ same residue
- IGF2 p.Pro173Leu Uncertain significance ★ ⚠ same residue
- IGF2 p.Pro173Ser Uncertain significance ★ ⚠ same residue
- IGF2 p.Pro173fs 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
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-pro173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown