Sugi Variant

Sugi Variant/TRIO

TRIO — 1955 ClinVar variants

All ClinVar germline TRIO variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 511 flagged for review →

77 Pathogenic · 17 Pathogenic/Likely pathogenic · 93 Likely pathogenic · 43 Conflicting · 166 Benign · 51 Benign/Likely benign · 474 Likely benign · 1034 Uncertain significance

Full TRIO gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 511

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 4

ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.

Predictors agree, ClinVar conflicts 27

ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.

Predicted LoF vs a conflicting call 5

ClinVar submitters conflict, and it's a predicted loss-of-function change in a gene where LoF causes disease — flagged for review, not resolved (verify NMD-escape for C-terminal truncations). Non-missense.

Predictors lean, ClinVar uncertain 404

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification. · showing the 150 best-reviewed of 404

Predictors split 71

The independent predictors disagree with each other — read with care.

All TRIO variants

Pathogenic 77

  • p.Gln280Ter Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Lys1431Met Multiple submitters Inborn genetic diseases
  • c.1732-1G>C Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.2046+1G>A Single submitter syndromic intellectual disability
  • c.347+1G>C Single submitter
  • c.4058+1G>A Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.4218+1G>A Single submitter
  • c.4614+1G>T Single submitter
  • c.5491_5496+12del Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.6084-2A>G Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg100fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg1078Gly Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Arg1195fs Single submitter
  • p.Arg1276Ter Single submitter
  • p.Arg1502Ter Single submitter
  • p.Arg2186fs Single submitter
  • p.Arg55Ter Single submitter
  • p.Arg948Ter Single submitter
  • p.Asn1080Ile Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Asp1790fs Single submitter Inborn genetic diseases
  • p.Asp2524fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Asp869fs Single submitter
  • p.Gln1139Ter Single submitter
  • p.Gln2193Ter Single submitter
  • p.Gln2535Ter Single submitter
  • p.Gln572Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln707Ter Single submitter
  • p.Gln787Ter Single submitter Inborn genetic diseases
  • p.Gln947Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu1299Lys Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu1438fs Single submitter Inborn genetic diseases
  • p.Glu1924fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu212Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu2362fs Single submitter
  • p.Glu273Ter Single submitter Inborn genetic diseases
  • p.Glu2801fs Single submitter Inborn genetic diseases
  • p.Glu379Ter Single submitter
  • p.Glu455fs Single submitter
  • p.Glu990Ter Single submitter Inborn genetic diseases
  • p.Gly1759fs Single submitter Inborn genetic diseases
  • p.Gly2297fs Single submitter
  • p.Gly2317fs Single submitter Inborn genetic diseases
  • p.Gly2396fs Single submitter Inborn genetic diseases
  • p.Gly2452fs Single submitter Inborn genetic diseases
  • p.His1469Arg Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.His2070fs Single submitter Inborn genetic diseases
  • p.His2347fs Single submitter
  • p.Leu1088fs Single submitter
  • p.Lys1086Glu Single submitter
  • p.Lys2163fs Single submitter Inborn genetic diseases
  • p.Met2588fs Single submitter
  • p.Phe2473fs Single submitter
  • p.Phe2609fs Single submitter
  • p.Pro1269fs Single submitter
  • p.Pro1461Thr Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Pro2350fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Ser2073Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Ser2315fs Single submitter
  • p.Ser2332fs Single submitter Inborn genetic diseases
  • p.Ser26Ter Single submitter
  • p.Thr1075Ala Single submitter
  • p.Trp1040Ter Single submitter Inborn genetic diseases
  • p.Trp1376Ter Single submitter TRIO-related disorder
  • p.Trp1582Ter Single submitter
  • p.Trp1776Ter Single submitter
  • p.Trp2788Ter Single submitter
  • p.Trp805Ter Single submitter
  • p.Tyr1017Ter Single submitter
  • p.Tyr1432Cys Single submitter
  • p.Val1014fs Single submitter
  • p.Val2134fs Single submitter
  • c.5203+1_5203+2dup No assertion criteria micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg217Ter No assertion criteria micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Asp1251fs No assertion criteria micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln1489fs No assertion criteria micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Ser475fs No assertion criteria micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Trp996Ter No assertion criteria

Pathogenic/Likely pathogenic 17

  • c.2391+1G>A Multiple submitters Inborn genetic diseases
  • c.6153+1G>A Multiple submitters Inborn genetic diseases
  • p.Ala2406fs Multiple submitters Inborn genetic diseases
  • p.Arg1078Gln Multiple submitters TRIO-related disorder
  • p.Arg1078Trp Multiple submitters intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Arg1411Ter Multiple submitters Autism Spectrum Disorder with Intellectual Disability
  • p.Arg1428Gln Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg1428Ter Multiple submitters
  • p.Arg1463Ter Multiple submitters intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Arg1505Ter Multiple submitters Autosomal dominant TRIO-related disorders
  • p.Arg217fs Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Asn1465Ser Multiple submitters intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Cys1220fs Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.His1371Arg Multiple submitters
  • p.Leu2031fs Multiple submitters TRIO-related disorder
  • p.Pro1461Arg Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Pro1461Leu Multiple submitters intellectual developmental disorder, autosomal dominant 63, with macrocephaly

Likely pathogenic 93

  • c.3447+2T>C Multiple submitters TRIO-related disorder
  • c.5497-1G>C Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg666Ter Multiple submitters TRIO-related disorder
  • p.Gln2343fs Multiple submitters TRIO-related disorder
  • p.Leu1434Phe Multiple submitters micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Tyr1362Cys Multiple submitters intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • c.232+1G>A Single submitter
  • c.2754+2T>C Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.3570+3G>A Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.3766-2A>C Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.5667+1G>A Single submitter TRIO-related disorder
  • c.5763+1G>T Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.5912+3A>G Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.6083_6083+1dup Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.6154-1G>A Single submitter
  • c.6466-1G>A Single submitter
  • c.7632+1G>T Single submitter TRIO-related disorder
  • c.8613-259C>T Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Ala2397fs Single submitter
  • p.Ala2454fs Single submitter
  • p.Ala253fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg100Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg1897fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg2053Ter Single submitter
  • p.Arg2187fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg2335fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg2404Ter Single submitter
  • p.Arg2525fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Arg2593Ter Single submitter
  • p.Asn857fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln1107Ter Single submitter autosomal recessive nonsyndromic hearing loss 28
  • p.Gln1191Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln284Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln383Ter Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Gln428Ter Single submitter
  • p.Gln564Ter Single submitter TRIO-related disorder
  • p.Gln573Ter Single submitter
  • p.Gln665Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln776Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gln854Arg Single submitter ⚠
  • p.Gln908Ter Single submitter TRIO-related disorder
  • p.Gln952fs Single submitter TRIO-related disorder
  • p.Gln954fs Single submitter
  • p.Glu1038Asp Single submitter ⚠
  • p.Glu1346Asp Single submitter ⚠
  • p.Glu1592Lys Single submitter TRIO-related disorder ⚠
  • p.Glu1828Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu2081Gln Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu2185fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Glu235fs Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Glu766fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gly1448Glu Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Gly2010fs Single submitter TRIO-related disorder
  • p.Gly2298fs Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.His376fs Single submitter TRIO-related disorder
  • p.Leu1071Pro Single submitter
  • p.Leu1124Ser Single submitter
  • p.Leu1894Ile Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome ⚠
  • p.Leu2468fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Leu408fs Single submitter TRIO-related disorder
  • p.Lys1388del Single submitter TRIO-related disorder
  • p.Lys1437Glu Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Lys1572= Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Lys2654Ter Single submitter Inborn genetic diseases
  • p.Met1873Ile Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Met60fs Single submitter Inborn genetic diseases
  • p.Phe1518fs Single submitter Neurodevelopmental delay
  • p.Phe1942fs Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Phe2029fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Pro1425Gln Single submitter
  • p.Ser1786fs Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Ser2440fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Ser2484fs Single submitter Deafness
  • p.Ser297Ter Single submitter
  • p.Thr1075Ile Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Thr1303Ile Single submitter intellectual disability
  • p.Thr1499fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Trp555_Gln556delinsCysTer Single submitter intellectual developmental disorder, autosomal dominant 63, with macrocephaly
  • p.Tyr1421His Single submitter
  • p.Tyr621fs Single submitter
  • p.Tyr621Ter Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Val1426Phe Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Val1985fs Single submitter micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • c.3331+2T>C No assertion criteria TRIO-related disorder
  • p.Ala2356fs No assertion criteria syndromic intellectual disability
  • p.Asn1947Asp No assertion criteria TRIO-related disorder ⚠
  • p.Gln854Ter No assertion criteria microcephaly
  • p.Glu2384fs No assertion criteria TRIO-related disorder
  • p.Gly2307fs No assertion criteria TRIO-related disorder
  • p.Leu881fs No assertion criteria micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
  • p.Met446Thr No assertion criteria Tip-toe gait
  • p.Pro2395fs No assertion criteria TRIO-related disorder
  • p.Trp1153Ter No assertion criteria TRIO-related disorder

Conflicting classifications of pathogenicity 43

Benign 166

Benign/Likely benign 51

Likely benign 474

Showing the top 300 by review status; the full set is in the sitemap.

Uncertain significance 1034

Showing the top 300 by review status; the full set is in the sitemap.