INS — 173 ClinVar variants
All ClinVar germline INS variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 52 flagged for review →
6 Pathogenic · 6 Pathogenic/Likely pathogenic · 21 Likely pathogenic · 28 Conflicting · 11 Benign · 11 Benign/Likely benign · 26 Likely benign · 64 Uncertain significance
Full INS gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 52
Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.
Predictors vs ClinVar 1
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
INS p.Ala24Val
Likely pathogenic
Multiple submitters
neonatal diabetes mellitus
Predictors agree, ClinVar conflicts 10
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
INS p.Ala23Thr
Conflicting
Single submitter
maturity-onset diabetes of the young type 10
-
INS p.Arg6His
Conflicting
Single submitter
INS-related disorder
-
INS p.Cys96Tyr
Conflicting
Single submitter
diabetes mellitus, permanent neonatal 4
-
INS p.Glu93Gly
Conflicting
Single submitter
monogenic diabetes
- INS p.Glu93Lys Conflicting Single submitter
-
INS p.Gly44Arg
Conflicting
Single submitter
Transient Neonatal Diabetes, Dominant/Recessive
- INS p.Gly75Asp Conflicting Single submitter
-
INS p.Ser76Asn
Conflicting
Single submitter
maturity-onset diabetes of the young type 10
-
INS p.Thr97Ser
Conflicting
Single submitter
maturity-onset diabetes of the young type 10
-
INS p.Tyr103Cys
Conflicting
Single submitter
diabetes mellitus, permanent neonatal 4
Predictors lean, ClinVar uncertain 22
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
INS p.Ala12Val
Uncertain significance
Multiple submitters
maturity-onset diabetes of the young type 10
-
INS p.Gly69Asp
Uncertain significance
Multiple submitters
INS-related disorder
-
INS p.Gly71Val
Uncertain significance
Multiple submitters
type 1 diabetes mellitus 2
-
INS p.Leu68Met
Uncertain significance
Multiple submitters
type 2 diabetes mellitus
-
INS p.Pro9Ser
Uncertain significance
Multiple submitters
INS-related disorder
- INS p.Cys31Gly Uncertain significance Single submitter
- INS p.Gln65Arg Uncertain significance Single submitter
-
INS p.Gln65Leu
Uncertain significance
Single submitter
type 1 diabetes mellitus 2
- INS p.Glu37Gly Uncertain significance Single submitter
-
INS p.Glu57Gly
Uncertain significance
Single submitter
type 1 diabetes mellitus 2
-
INS p.Glu67Val
Uncertain significance
Single submitter
type 1 diabetes mellitus 2
-
INS p.Gly70Arg
Uncertain significance
Single submitter
type 1 diabetes mellitus 2
- INS p.Gly71Ala Uncertain significance Single submitter
-
INS p.Gly84Arg
Uncertain significance
Single submitter
diabetes mellitus, permanent neonatal 4
-
INS p.Gly90Cys
Uncertain significance
Single submitter
diabetes mellitus, permanent neonatal 4
- INS p.Ile91Thr Uncertain significance Single submitter
- INS p.Leu10Gln Uncertain significance Single submitter
- INS p.Pro72Leu Uncertain significance Single submitter
- INS p.Ser101Tyr Uncertain significance Single submitter
- INS p.Val63Ala Uncertain significance Single submitter
-
INS p.Val92Leu
Uncertain significance
Single submitter
diabetes mellitus, permanent neonatal 4
-
INS p.Ala81Val
Uncertain significance
No assertion criteria
INS-related disorder
Predictors split 19
The independent predictors disagree with each other — read with care.
-
INS p.Gly32Ser
Pathogenic/Likely pathogenic
Multiple submitters
INS-related disorders
-
INS p.Ala15Asp
Uncertain significance
Single submitter
type 1 diabetes mellitus 2
-
INS p.Arg46Gln
Conflicting
Single submitter
INS-related disorders
- INS p.Arg55His Uncertain significance Single submitter
- INS p.Cys100Tyr Uncertain significance Single submitter
-
INS p.Cys95Arg
Likely pathogenic
Single submitter
diabetes mellitus, permanent neonatal 4
-
INS p.Cys95Tyr
Likely pathogenic
Single submitter
INS-related disorder
- INS p.Glu106Val Uncertain significance Single submitter
-
INS p.Gly47Val
Uncertain significance
Single submitter
diabetes mellitus, permanent neonatal 4
-
INS p.His29Asp
Uncertain significance
Single submitter
diabetes mellitus, permanent neonatal 4
- INS p.His34Arg Uncertain significance Single submitter
-
INS p.His34Asp
Uncertain significance
Single submitter
hyperproinsulinemia
-
INS p.His34Pro
Likely pathogenic
Single submitter
neonatal diabetes mellitus
-
INS p.Lys53Glu
Uncertain significance
Single submitter
type 1 diabetes mellitus 2
-
INS p.Pro52Arg
Likely pathogenic
Single submitter
Neonatal insulin-dependent diabetes mellitus
-
INS p.Pro52His
Uncertain significance
Single submitter
maturity-onset diabetes of the young type 10
- INS p.Ser85Cys Uncertain significance Single submitter
-
INS p.Phe48Ser
Pathogenic
No assertion criteria
hyperproinsulinemia
-
INS p.Phe49Leu
Pathogenic
No assertion criteria
hyperproinsulinemia
All INS variants
Pathogenic 6
- c.-152C>G Multiple submitters diabetes mellitus, permanent neonatal 4
- c.-33A>G Single submitter maturity-onset diabetes of the young type 10
- p.Arg89Leu No assertion criteria hyperproinsulinemia
- p.Arg89Pro No assertion criteria hyperproinsulinemia
- p.Phe48Ser No assertion criteria hyperproinsulinemia ⚠
- p.Phe49Leu No assertion criteria hyperproinsulinemia ⚠
Pathogenic/Likely pathogenic 6
- c.-152C>A Multiple submitters diabetes mellitus, permanent neonatal 4
- p.Arg89Cys Multiple submitters INS-related disorders
- p.Arg89His Multiple submitters INS-related disorder
- p.Gly32Ser Multiple submitters INS-related disorders ⚠
- p.Met1Val Multiple submitters type 1 diabetes mellitus 2
- p.Val42Ala Multiple submitters maturity-onset diabetes of the young type 10
Likely pathogenic 21
- p.Ala24Val Multiple submitters neonatal diabetes mellitus ⚠
- c.*59A>G Single submitter hyperproinsulinemia
- p.Arg46Ter Single submitter INS-related disorder
- p.Cys109Phe Single submitter neonatal diabetes mellitus
- p.Cys109Tyr Single submitter maturity-onset diabetes of the young type 10
- p.Cys43Trp Single submitter
- p.Cys95Arg Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.Cys95Tyr Single submitter INS-related disorder ⚠
- p.Glu59fs Single submitter Neonatal insulin-dependent diabetes mellitus
- p.Gly32Val Single submitter
- p.His34Pro Single submitter neonatal diabetes mellitus ⚠
- p.Leu105Val Single submitter permanent neonatal diabetes mellitus
- p.Leu35Met Single submitter neonatal diabetes mellitus
- p.Leu35Val Single submitter
- p.Leu39Phe Single submitter maturity-onset diabetes of the young type 10
- p.Pro52Arg Single submitter Neonatal insulin-dependent diabetes mellitus ⚠
- p.Ser98Ile Single submitter neonatal diabetes mellitus
- p.Thr97Pro Single submitter
- p.Tyr108Asp Single submitter neonatal diabetes mellitus
- p.Val42Gly Single submitter maturity-onset diabetes of the young type 10
- p.Cys43Ter No assertion criteria maturity-onset diabetes of the young type 10
Conflicting classifications of pathogenicity 28
- c.187+241G>A Single submitter diabetes mellitus, permanent neonatal 4
- c.188-3C>A Single submitter Transient Neonatal Diabetes, Dominant/Recessive
- c.188-96G>A Single submitter Neonatal insulin-dependent diabetes mellitus
- c.-153C>G Single submitter maturity-onset diabetes of the young type 10
- c.-17-70G>A Single submitter Neonatal insulin-dependent diabetes mellitus
- c.-18+22G>A Single submitter Neonatal insulin-dependent diabetes mellitus
- c.-18+3C>G Single submitter Transient Neonatal Diabetes, Dominant/Recessive
- c.-18+4_-18+5insTTGC Single submitter maturity-onset diabetes of the young type 10
- c.-39A>C Single submitter Neonatal insulin-dependent diabetes mellitus
- c.*22A>C Single submitter diabetes mellitus, permanent neonatal 4
- c.*28G>A Single submitter Transient Neonatal Diabetes, Dominant/Recessive
- c.*2C>T Single submitter Transient Neonatal Diabetes, Dominant/Recessive
- c.*42C>T Single submitter Transient Neonatal Diabetes, Dominant/Recessive
- p.Ala23Thr Single submitter maturity-onset diabetes of the young type 10 ⚠
- p.Arg46Gln Single submitter INS-related disorders ⚠
- p.Arg6His Single submitter INS-related disorder ⚠
- p.Cys96Tyr Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.Glu93Gly Single submitter monogenic diabetes ⚠
- p.Glu93Lys Single submitter ⚠
- p.Gly44_Phe48del Single submitter Neonatal insulin-dependent diabetes mellitus
- p.Gly44Arg Single submitter Transient Neonatal Diabetes, Dominant/Recessive ⚠
- p.Gly75Asp Single submitter ⚠
- p.Phe49= Single submitter hyperproinsulinemia
- p.Pro21= Single submitter Inborn genetic diseases
- p.Ser76Asn Single submitter maturity-onset diabetes of the young type 10 ⚠
- p.Thr97Ser Single submitter maturity-onset diabetes of the young type 10 ⚠
- p.Tyr103Cys Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.Tyr108del Single submitter Neonatal insulin-dependent diabetes mellitus
Benign 11
- c.-17-6T>A Multiple submitters maturity-onset diabetes of the young type 10
- c.-18+38A>G Multiple submitters
- c.-463_-451del Multiple submitters
- c.187+15C>T Single submitter Neonatal insulin-dependent diabetes mellitus
- c.188-111C>T Single submitter
- c.188-11C>T Single submitter
- c.188-168G>C Single submitter
- c.-379_-372dup Single submitter
- c.-449_-443del Single submitter
- c.-485_-430del Single submitter
- c.*30C>T Single submitter
Benign/Likely benign 11
- c.187+11T>C Multiple submitters maturity-onset diabetes of the young type 10
- c.188-10G>A Multiple submitters maturity-onset diabetes of the young type 10
- c.188-16C>T Multiple submitters type 1 diabetes mellitus 2
- c.188-220C>T Multiple submitters Neonatal insulin-dependent diabetes mellitus
- c.-147del Multiple submitters Neonatal insulin-dependent diabetes mellitus
- c.-18+21C>T Multiple submitters Neonatal insulin-dependent diabetes mellitus
- c.-9C>T Multiple submitters diabetes mellitus, permanent neonatal 4
- c.*9C>T Multiple submitters maturity-onset diabetes of the young type 10
- p.Ala12= Multiple submitters diabetes mellitus, permanent neonatal 4
- p.Ala24= Multiple submitters Transient Neonatal Diabetes, Dominant/Recessive
- p.Thr51= Multiple submitters Inborn genetic diseases
Likely benign 26
- p.Cys43= Multiple submitters
- c.187+203G>A Single submitter
- c.187+282G>A Single submitter
- c.187+8A>G Single submitter
- c.188-114G>T Single submitter
- c.188-11C>A Single submitter
- c.188-17G>A Single submitter
- c.188-18C>T Single submitter
- c.188-32C>T Single submitter
- c.188-40C>T Single submitter
- c.-146A>C Single submitter
- p.Ala2= Single submitter
- p.Ala22= Single submitter Neonatal insulin-dependent diabetes mellitus
- p.Cys31= Single submitter
- p.Glu83= Single submitter
- p.Glu93= Single submitter
- p.Gly69= Single submitter
- p.Gly73= Single submitter
- p.Leu16= Single submitter
- p.Leu68= Single submitter Inborn genetic diseases
- p.Tyr50= Single submitter Inborn genetic diseases
- p.Val63= Single submitter
- c.187+245C>T No assertion criteria INS-related disorder
- c.187+391C>T No assertion criteria
- c.187+6C>G No assertion criteria INS-related disorder
- c.*49G>A No assertion criteria INS-related disorder
Uncertain significance 64
- c.187+3G>A Multiple submitters type 1 diabetes mellitus 2
- c.188-5_188-4insGCGCAGTGGGGCACCTGCCACTGCGC Multiple submitters
- c.-152C>T Multiple submitters hyperproinsulinemia
- c.-18+62C>T Multiple submitters Neonatal insulin-dependent diabetes mellitus
- c.-187_-164del Multiple submitters diabetes mellitus, permanent neonatal 4
- p.Ala12Val Multiple submitters maturity-onset diabetes of the young type 10 ⚠
- p.Gly69Asp Multiple submitters INS-related disorder ⚠
- p.Gly71Val Multiple submitters type 1 diabetes mellitus 2 ⚠
- p.Leu68Met Multiple submitters type 2 diabetes mellitus ⚠
- p.Pro9Ser Multiple submitters INS-related disorder ⚠
- c.187+11_187+12inv Single submitter
- c.187+15C>A Single submitter maturity-onset diabetes of the young type 10
- c.187+223G>A Single submitter
- c.187+241G>C Single submitter
- c.187+271A>G Single submitter
- c.188-137A>T Single submitter
- c.188-15G>A Single submitter
- c.188-16C>A Single submitter type 1 diabetes mellitus 2
- c.188-233C>T Single submitter
- c.188-43C>T Single submitter INS-related disorder
- c.188-97C>T Single submitter
- c.-17-74T>C Single submitter
- c.-293C>T Single submitter
- c.-439G>A Single submitter
- c.-46A>G Single submitter
- c.-83G>A Single submitter
- c.-88A>G Single submitter
- c.*34T>A Single submitter maturity-onset diabetes of the young type 10
- p.Ala15Asp Single submitter type 1 diabetes mellitus 2 ⚠
- p.Ala81fs Single submitter
- p.Arg55His Single submitter ⚠
- p.Cys100Tyr Single submitter ⚠
- p.Cys31Gly Single submitter ⚠
- p.Gln104Ter Single submitter
- p.Gln65Arg Single submitter ⚠
- p.Gln65Leu Single submitter type 1 diabetes mellitus 2 ⚠
- p.Gln65Ter Single submitter
- p.Glu106del Single submitter
- p.Glu106Val Single submitter ⚠
- p.Glu37Gly Single submitter ⚠
- p.Glu57Gly Single submitter type 1 diabetes mellitus 2 ⚠
- p.Glu67Val Single submitter type 1 diabetes mellitus 2 ⚠
- p.Gly47Val Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.Gly70Arg Single submitter type 1 diabetes mellitus 2 ⚠
- p.Gly71Ala Single submitter ⚠
- p.Gly84Arg Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.Gly90Cys Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.His29Asp Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.His34Arg Single submitter ⚠
- p.His34Asp Single submitter hyperproinsulinemia ⚠
- p.Ile91Thr Single submitter ⚠
- p.Leu10Gln Single submitter ⚠
- p.Lys53Glu Single submitter type 1 diabetes mellitus 2 ⚠
- p.Lys53Thr Single submitter type 1 diabetes mellitus 2
- p.Met1Ile Single submitter diabetes mellitus, permanent neonatal 4
- p.Met5Ile Single submitter
- p.Pro52His Single submitter maturity-onset diabetes of the young type 10 ⚠
- p.Pro72Leu Single submitter ⚠
- p.Ser101Tyr Single submitter ⚠
- p.Ser85Cys Single submitter ⚠
- p.Thr51Ile Single submitter
- p.Val63Ala Single submitter ⚠
- p.Val92Leu Single submitter diabetes mellitus, permanent neonatal 4 ⚠
- p.Ala81Val No assertion criteria INS-related disorder ⚠