IGF1 p.Lys134=
c.402G>A · rs776125139 · VCV1430976
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00144%, nfe)
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 7.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 21.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00144%
European (non-Finnish) · 17/1,179,512 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000718%
Overall
0.00105%
17/1,612,374 alleles · very rare
exomes 16/1,460,232 · genomes 1/152,142 · joint denominator
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.Lys134=
- Coding
- c.402G>A
- MANE Select
- NM_000618
- dbSNP
- rs776125139
- Type
- single nucleotide variant
- Location
- chr12:102419509 (GRCh38)
- Gene constraint
- LOEUF 0.675 · pLI 0.76 (gnomAD)
- Structure
- AlphaFold pLDDT 59.69 · 32 PDB
- Residue 134
- the 'disordered' region
Similar variants
- IGF1 p.Lys134Arg 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-lys134 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown