IGF1 p.Ala86=
c.258G>A · rs766050142 · VCV2178898
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, 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 -9.7 | GERP -5.4 |
| Overall | ||
| CADD | 0.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,914 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.00304%
49/1,613,098 alleles · ultra-rare
exomes 39/1,460,954 · genomes 10/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,364 |
| South Asian | 0.00549% | 18,215 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| Finnishnot grpmax-eligible | 0.00475% | 21,047 |
| European (non-Finnish) | 0.00246% | 40,690 |
| Admixed American | 0.00167% | 60,000 |
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.Ala86=
- Coding
- c.258G>A
- MANE Select
- NM_000618
- dbSNP
- rs766050142
- Type
- single nucleotide variant
- Location
- chr12:102419653 (GRCh38)
- Gene constraint
- LOEUF 0.675 · pLI 0.76 (gnomAD)
- Structure
- AlphaFold pLDDT 59.69 · 32 PDB
- Residue 86
- the 'c' region
Similar variants
- IGF1 p.Ala86Val Uncertain significance ★ ⚠ same residue
- 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
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-ala86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown