IGF1 p.Cys54=
c.162C>T · rs766707179 · VCV1674648
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 -0.86 | GERP -3.7 |
| Overall | ||
| CADD | 9.557 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,078 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000805%
13/1,614,050 alleles · very rare
exomes 11/1,461,872 · genomes 2/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,769 |
| African / African-American | 0.00267% | 37,461 |
| Admixed American | 0.00167% | 59,998 |
| European (non-Finnish) | 0.000508% | 196,675 |
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.Cys54=
- Coding
- c.162C>T
- MANE Select
- NM_000618
- dbSNP
- rs766707179
- Type
- single nucleotide variant
- Location
- chr12:102475701 (GRCh38)
- Gene constraint
- LOEUF 0.675 · pLI 0.76 (gnomAD)
- Structure
- AlphaFold pLDDT 59.69 · 32 PDB
- Residue 54
- a disulfide bond; an α-helix; the 'b' region
Similar variants
- IGF1 p.Cys54Trp 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.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-cys54 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown