IGF2 p.Ser8=
c.24G>A · VCV4707336
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.9, phastCons 1 |
| Overall | ||
| CADD | 16.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,936 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000682%
11/1,613,422 alleles · very rare
exomes 6/1,461,180 · genomes 5/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,979 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,231 |
| European (non-Finnish) | 0.000509% | 196,636 |
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.Ser8=
- Coding
- c.24G>A
- MANE Select
- NM_000612
- Type
- single nucleotide variant
- Location
- chr11:2135500 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.96 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.95 · 16 PDB
Similar variants
- IGF2 p.Ser8Ter Pathogenic 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-ser8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown