Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.77%, afr)
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 -8 | GERP -3.7 |
| Overall | ||
| CADD | 1.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.77%
African / African-American · 578/75,064 alleles
Filtering AF
0.718%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.697%
Overall
0.0385%
622/1,614,208 alleles · rare
exomes 301/1,461,884 · genomes 321/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.77% | 130 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,718 |
| Admixed American | 0.0217% | 4,618 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000593% | 168,577 |
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
- IGF1
- Protein
- p.Thr52=
- Coding
- c.156G>A
- MANE Select
- NM_000618
- dbSNP
- rs3729846
- Type
- single nucleotide variant
- Location
- chr12:102475707 (GRCh38)
- Gene constraint
- LOEUF 0.675 · pLI 0.76 (gnomAD)
- Structure
- AlphaFold pLDDT 59.69 · 32 PDB
- Residue 52
- an α-helix; the 'b' region
Similar variants
- IGF1 c.*260A>T Uncertain significance ★★ same type
- IGF1 p.Ala115Val Uncertain significance ★★ ⚠ same type
- IGF1 p.Arg119His Uncertain significance ★★ ⚠ same type
- IGF1 p.Arg122His Uncertain significance ★★ ⚠ same type
- IGF1 p.Cys54Trp Uncertain significance ★★ ⚠ same type
- IGF1 p.Leu7Phe Uncertain significance ★★ ⚠ same type
- IGF1 c.402+1663C>A Likely benign ★★ same type
- IGF1 c.*105T>C Likely benign ★★ 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/igf1-p-thr52 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown