IGF2 p.Ala148=
c.444G>A · rs781299823 · VCV728165
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00442%, 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 -0.001 | GERP -1.7, phastCons 0.044 |
| Overall | ||
| CADD | 5.564 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00442%
South Asian · 4/90,554 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000895%
Overall
0.00137%
22/1,607,822 alleles · very rare
exomes 20/1,455,486 · genomes 2/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00442% | 22,639 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0034% | 29,404 |
| European (non-Finnish) | 0.00144% | 69,230 |
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.Ala148=
- Coding
- c.444G>A
- MANE Select
- NM_000612
- dbSNP
- rs781299823
- Type
- single nucleotide variant
- Location
- chr11:2133086 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
- Residue 148
- a UniProt-annotated variant site (in srs3)
Similar variants
- IGF2 p.Ala148Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown