IGF1R p.Pro233=
c.699C>T · rs17847196 · VCV2645731
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.178%, eas)
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 -10 | GERP -4.2 |
| Overall | ||
| CADD | 6.474 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.178%
East Asian · 80/44,862 alleles
Filtering AF
0.147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.135%
Overall
0.00707%
114/1,612,112 alleles · rare
exomes 109/1,459,878 · genomes 5/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.178% | 561 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| African / African-American | 0.00267% | 37,505 |
| European (non-Finnish) | 0.00237% | 42,142 |
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
- IGF1R
- Protein
- p.Pro233=
- Coding
- c.699C>T
- MANE Select
- NM_000875
- dbSNP
- rs17847196
- Type
- single nucleotide variant
- Location
- chr15:98891383 (GRCh38)
- Gene constraint
- LOEUF 0.393 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 46 PDB
Similar variants
- IGF1R c.3187-2A>T Likely pathogenic ★★ same type
- IGF1R c.3457+1G>A Pathogenic/Likely pathogenic ★★ same type
- IGF1R c.641-2A>G Pathogenic ★★ same type
- IGF1R p.Arg365Ter Pathogenic/Likely pathogenic ★★ same type
- IGF1R p.Arg753Ter Pathogenic/Likely pathogenic ★★ same type
- IGF1R p.Cys307Ter Pathogenic ★★ same type
- IGF1R p.Gly1152Arg Pathogenic/Likely pathogenic ★★ same type
- IGF1R c.1102+6T>C 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/igf1r-p-pro233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown