IGFBP7 p.Pro187=
c.561G>A · rs35855328 · VCV791477
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.22%, 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 -0.44 | GERP -4.4, phastCons 0.17 |
| Overall | ||
| CADD | 7.181 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.22%
European (non-Finnish) · 14,416/1,179,052 alleles
Filtering AF
1.21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.2%
Overall
1.03%
16,576/1,613,072 alleles · low-frequency
exomes 15,459/1,460,754 · genomes 1,117/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.22% | 82 |
| Finnishnot grpmax-eligible | 1.01% | 99 |
| Ashkenazi Jewishnot grpmax-eligible | 0.872% | 115 |
| Remaining individualsnot grpmax-eligible | 0.82% | 122 |
| South Asian | 0.456% | 219 |
| Admixed American | 0.323% | 309 |
| African / African-American | 0.168% | 595 |
| Middle Eastern | 0.116% | 864 |
| East Asian | 0.00223% | 44,874 |
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
- IGFBP7
- Protein
- p.Pro187=
- Coding
- c.561G>A
- MANE Select
- NM_001553
- dbSNP
- rs35855328
- Type
- single nucleotide variant
- Location
- chr4:57040848 (GRCh38)
- Gene constraint
- LOEUF 1.812 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.11 · 3 PDB
- Residue 187
- the ig-like c2-type domain
Similar variants
- IGFBP7 c.830-1G>A Pathogenic/Likely pathogenic ★★ same type
- IGFBP7 c.585+4T>A Benign ★★ same type
- IGFBP7 c.703-10T>C Benign ★★ same type
- IGFBP7 p.Ala101Val Uncertain significance ★ ⚠ same type
- IGFBP7 p.Ala136Thr Uncertain significance ★ ⚠ same type
- IGFBP7 p.Ala56Glu Uncertain significance ★ ⚠ same type
- IGFBP7 p.Ala56Gly Uncertain significance ★ ⚠ same type
- IGFBP7 p.Ala56Val 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/igfbp7-p-pro187 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown