IGF2 p.Leu142=
c.426C>T · VCV3672368
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 0.05 | GERP -1.6, phastCons 0.39 |
| Overall | ||
| CADD | 3.499 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,026 alleles
Filtering AF
0.00972%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00907%
Overall
0.00921%
148/1,607,800 alleles · ultra-rare
exomes 136/1,455,470 · genomes 12/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,026 |
| European (non-Finnish) | 0.0113% | 8,847 |
| Remaining individualsnot grpmax-eligible | 0.00804% | 12,434 |
| African / African-American | 0.00534% | 18,725 |
| Finnishnot grpmax-eligible | 0.00475% | 21,055 |
| Admixed American | 0.00169% | 59,346 |
| South Asian | 0.0011% | 90,594 |
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.Leu142=
- Coding
- c.426C>T
- MANE Select
- NM_000612
- Type
- single nucleotide variant
- Location
- chr11:2133104 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
- Residue 142
- a UniProt-annotated variant site (in srs3)
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-leu142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown