INSR p.Pro987=
c.2961G>T · VCV4940226
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000607%, 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 -20 | GERP -3 |
| Overall | ||
| CADD | 0.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000607%
European (non-Finnish) · 7/1,153,168 alleles
Filtering AF
0.000252%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000162%
Overall
0.000447%
7/1,565,052 alleles · very rare
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
- INSR
- Protein
- p.Pro987=
- Coding
- c.2961G>T
- MANE Select
- NM_000208
- Type
- single nucleotide variant
- Location
- chr19:7126636 (GRCh38)
- Gene constraint
- LOEUF 0.556 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.35 · 94 PDB
- Residue 987
- a UniProt-annotated variant site (in leprch)
Similar variants
- INSR p.Pro987Leu Uncertain significance ★★ ⚠ same residue
- INSR p.Ala1055Val Likely pathogenic ★★ same type
- INSR p.Arg1020Gln Likely pathogenic ★★ same type
- INSR p.Arg1020Ter Pathogenic ★★ same type
- INSR p.Arg1027Ter Pathogenic ★★ same type
- INSR p.Arg1201Gln Pathogenic ★★ same type
- INSR p.Arg525Ter Likely pathogenic ★★ same type
- INSR p.His236Arg Pathogenic/Likely pathogenic ★★ 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/insr-p-pro987 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown