NOTCH4 — 326 ClinVar variants

All ClinVar germline NOTCH4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 213 flagged for review →

1 Conflicting · 83 Benign · 2 Benign/Likely benign · 20 Likely benign · 220 Uncertain significance

Full NOTCH4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 213

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 agree, ClinVar conflicts 1

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

NOTCH4 p.Pro1194Leu Conflicting Single submitter

Predictors lean, ClinVar uncertain 182

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 182

Predictors split 30

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

All NOTCH4 variants

Conflicting classifications of pathogenicity 1

p.Pro1194Leu Single submitter ⚠

Benign 83

p.Ala526= Multiple submitters
p.Leu1610= Multiple submitters
p.Leu16del Multiple submitters
c.1160-38G>A Single submitter
c.1315+67_1315+68dup Single submitter
c.1316-158T>A Single submitter
c.1316-159G>A Single submitter
c.1316-42T>C Single submitter
c.1316-74C>A Single submitter
c.1510+167A>G Single submitter
c.1511-165C>T Single submitter
c.1511-39_1511-38del Single submitter
c.1511-7T>A Single submitter
c.156-37A>G Single submitter
c.1624+167C>T Single submitter
c.1625-203A>C Single submitter
c.1861+148C>T Single submitter
c.1861+17C>T Single submitter
c.1862-13C>T Single submitter
c.2021+128A>G Single submitter
c.2022-229A>G Single submitter
c.2321-153C>T Single submitter
c.2527-27T>A Single submitter
c.2680+105T>C Single submitter
c.2680+10G>A Single submitter
c.2681-189A>G Single submitter
c.2681-60A>G Single submitter
c.2865+9G>T Single submitter
c.3119-24A>G Single submitter
c.3231+179A>G Single submitter
c.3232-31G>C Single submitter
c.3232-57G>A Single submitter
c.3232-89del Single submitter
c.4316-87C>A Single submitter
c.451+71A>G Single submitter
c.4617+42G>C Single submitter
c.4618-44G>C Single submitter
c.4756+37del Single submitter
c.4757-212C>T Single submitter
c.4757-73T>C Single submitter
c.5053-20C>G Single submitter
c.5053-25G>T Single submitter
c.5200+36del Single submitter
c.73+13G>A Single submitter
c.73+176C>T Single submitter
c.73+26G>A Single submitter
c.73+52A>T Single submitter
c.73+89G>A Single submitter
c.74-178C>T Single submitter
c.74-8A>T Single submitter
c.-117C>T Single submitter
p.Ala190= Single submitter
p.Asp1984= Single submitter
p.Asp272Gly Single submitter
p.Gln1809= Single submitter
p.Gln284= Single submitter
p.Gln622= Single submitter
p.Gly1099Arg Single submitter ⚠
p.Gly111= Single submitter
p.Gly1213Arg Single submitter
p.Gly1701= Single submitter
p.Gly1854= Single submitter
p.Gly348= Single submitter
p.Gly534Ser Single submitter
p.Gly942Arg Single submitter
p.Gly989= Single submitter
p.Leu13_Leu16del Single submitter
p.Leu15_Leu16dup Single submitter
p.Leu16dup Single submitter
p.Leu215= Single submitter
p.Lys117Gln Single submitter
p.Phe186= Single submitter
p.Pro204Leu Single submitter
p.Pro271= Single submitter
p.Pro85= Single submitter
p.Ser100Asn Single submitter ⚠
p.Ser1895= Single submitter
p.Ser244Leu Single submitter
p.Thr1367= Single submitter
p.Thr174= Single submitter
p.Thr320Ala Single submitter
p.Thr684= Single submitter
p.Val1384= Single submitter

Benign/Likely benign 2

p.Cys815Gly Multiple submitters Anophthalmia-microphthalmia syndrome
p.Gln1469= Multiple submitters

Likely benign 20

p.Val600Leu Multiple submitters
c.2527-8C>T Single submitter
c.5299-3C>G Single submitter
p.Ala1250Thr Single submitter
p.Arg132His Single submitter
p.Asp1309= Single submitter
p.Asp1695Asn Single submitter
p.Asp404Glu Single submitter
p.Asp553Asn Single submitter
p.Gly267= Single submitter
p.Gly796= Single submitter
p.Leu12_Leu16del Single submitter
p.Leu1319= Single submitter
p.Leu1900Phe Single submitter
p.Met946Val Single submitter
p.Phe64Ile Single submitter
p.Pro184= Single submitter
p.Pro800= Single submitter
p.Ser1961Pro Single submitter
p.Thr496= Single submitter

Uncertain significance 220

c.5299-1G>A Single submitter congenital anomaly of kidney and urinary tract
c.5299-1G>T Single submitter
p.Ala1022Thr Single submitter ⚠
p.Ala1027Asp Single submitter ⚠
p.Ala1088Val Single submitter ⚠
p.Ala1307Pro Single submitter ⚠
p.Ala1314Val Single submitter ⚠
p.Ala1347Thr Single submitter ⚠
p.Ala1417Thr Single submitter ⚠
p.Ala1496Pro Single submitter ⚠
p.Ala1608Glu Single submitter ⚠
p.Ala1737Val Single submitter ⚠
p.Ala1747Asp Single submitter ⚠
p.Ala1775Gly Single submitter
p.Ala1802Glu Single submitter ⚠
p.Ala1807Thr Single submitter ⚠
p.Ala1822Thr Single submitter ⚠
p.Ala1831Thr Single submitter ⚠
p.Ala1837Thr Single submitter ⚠
p.Ala1837Val Single submitter ⚠
p.Ala362Val Single submitter ⚠
p.Ala365Gly Single submitter ⚠
p.Ala610Gly Single submitter ⚠
p.Ala659Val Single submitter ⚠
p.Ala71Thr Single submitter ⚠
p.Ala82Thr Single submitter ⚠
p.Ala86Pro Single submitter ⚠
p.Ala889Thr Single submitter ⚠
p.Ala943Val Single submitter ⚠
p.Ala947Gly Single submitter ⚠
p.Ala947Val Single submitter ⚠
p.Arg1113His Single submitter ⚠
p.Arg1113Leu Single submitter ⚠
p.Arg1169Trp Single submitter ⚠
p.Arg1219Leu Single submitter ⚠
p.Arg1317Gln Single submitter ⚠
p.Arg1317Trp Single submitter ⚠
p.Arg1333Pro Single submitter ⚠
p.Arg1355Gln Single submitter ⚠
p.Arg1355Trp Single submitter ⚠
p.Arg1400Cys Single submitter ⚠
p.Arg1400His Single submitter ⚠
p.Arg1472Gln Single submitter ⚠
p.Arg1476Gln Single submitter ⚠
p.Arg1476Ter Single submitter
p.Arg1492Gln Single submitter ⚠
p.Arg1492Gly Single submitter ⚠
p.Arg1499Gln Single submitter ⚠
p.Arg1499Gly Single submitter ⚠
p.Arg1583His Single submitter ⚠
p.Arg1643Ter Single submitter
p.Arg1646Gln Single submitter ⚠
p.Arg1680Leu Single submitter ⚠
p.Arg1680Trp Single submitter ⚠
p.Arg1688Cys Single submitter ⚠
p.Arg1835His Single submitter ⚠
p.Arg1842Cys Single submitter ⚠
p.Arg1871His Single submitter ⚠
p.Arg1898Gln Single submitter ⚠
p.Arg1915Met Single submitter ⚠
p.Arg1931Gln Single submitter ⚠
p.Arg1940Cys Single submitter ⚠
p.Arg471His Single submitter ⚠
p.Arg807Cys Single submitter ⚠
p.Arg829Cys Single submitter ⚠
p.Asn1265Asp Single submitter ⚠
p.Asn533Lys Single submitter ⚠
p.Asn562Asp Single submitter
p.Asn632Ile Single submitter ⚠
p.Asn740Tyr Single submitter ⚠
p.Asn903Ser Single submitter ⚠
p.Asp1012His Single submitter ⚠
p.Asp1184Asn Single submitter ⚠
p.Asp1375Asn Single submitter ⚠
p.Asp1715Asn Single submitter ⚠
p.Asp1948Gly Single submitter ⚠
p.Asp680Asn Single submitter ⚠
p.Asp909Glu Single submitter
p.Cys105Tyr Single submitter ⚠
p.Cys1597Arg Single submitter ⚠
p.Cys302Tyr Single submitter ⚠
p.Cys341Tyr Single submitter ⚠
p.Cys463Arg Single submitter ⚠
p.Cys484Tyr Single submitter ⚠
p.Cys613Trp Single submitter ⚠
p.Gln1360Arg Single submitter ⚠
p.Gln1763Lys Single submitter ⚠
p.Gln635His Single submitter ⚠
p.Gln69Glu Single submitter ⚠
p.Gln850Arg Single submitter ⚠
p.Gln872His Single submitter ⚠
p.Gln893Lys Single submitter ⚠
p.Glu1269Lys Single submitter ⚠
p.Glu1422Gln Single submitter ⚠
p.Glu1506Lys Single submitter ⚠
p.Glu1522Asp Single submitter ⚠
p.Glu197Lys Single submitter ⚠
p.Glu313Ala Single submitter ⚠
p.Glu313Lys Single submitter ⚠
p.Glu354Val Single submitter ⚠
p.Glu513Gly Single submitter ⚠
p.Glu516Asp Single submitter ⚠
p.Gly1092Ser Single submitter ⚠
p.Gly1167Arg Single submitter ⚠
p.Gly1201Arg Single submitter ⚠
p.Gly1266Arg Single submitter ⚠
p.Gly1380Arg Single submitter ⚠
p.Gly1559Glu Single submitter ⚠
p.Gly1757Arg Single submitter ⚠
p.Gly1890Trp Single submitter ⚠
p.Gly1891Cys Single submitter ⚠
p.Gly1913Ala Single submitter ⚠
p.Gly208Ser Single submitter ⚠
p.Gly349Cys Single submitter ⚠
p.Gly367Glu Single submitter ⚠
p.Gly403Ala Single submitter ⚠
p.Gly423Ser Single submitter ⚠
p.Gly670Arg Single submitter ⚠
p.Gly905Ser Single submitter ⚠
p.His1217Arg Single submitter ⚠
p.His1478Leu Single submitter ⚠
p.His189Arg Single submitter ⚠
p.His402Gln Single submitter ⚠
p.Ile1047Thr Single submitter ⚠
p.Leu1297Pro Single submitter ⚠
p.Leu1308Pro Single submitter
p.Leu1351Val Single submitter ⚠
p.Leu1619Met Single submitter arteriovenous malformations of the brain ⚠
p.Leu1687Phe Single submitter
p.Leu1705Val Single submitter ⚠
p.Leu1972Pro Single submitter ⚠
p.Leu44Pro Single submitter ⚠
p.Leu532Phe Single submitter ⚠
p.Leu623Val Single submitter ⚠
p.Leu844Val Single submitter ⚠
p.Lys1107Arg Single submitter ⚠
p.Lys1176Asn Single submitter ⚠
p.Lys637Asn Single submitter ⚠
p.Met1592Leu Single submitter
p.Phe1381Ser Single submitter ⚠
p.Phe1840Leu Single submitter ⚠
p.Phe990Tyr Single submitter ⚠
p.Pro1054Leu Single submitter ⚠
p.Pro1068Ser Single submitter ⚠
p.Pro1131Leu Single submitter ⚠
p.Pro1253Leu Single submitter ⚠
p.Pro1286His Single submitter ⚠
p.Pro1357Leu Single submitter ⚠
p.Pro1428Leu Single submitter ⚠
p.Pro1440Ser Single submitter ⚠
p.Pro1545Leu Single submitter ⚠
p.Pro1590Thr Single submitter ⚠
p.Pro1618Leu Single submitter ⚠
p.Pro1833Thr Single submitter ⚠
p.Pro184Leu Single submitter ⚠
p.Pro1974Ser Single submitter ⚠
p.Pro240Arg Single submitter ⚠
p.Pro323Ser Single submitter ⚠
p.Pro366Leu Single submitter ⚠
p.Pro400Leu Single submitter ⚠
p.Pro584Thr Single submitter ⚠
p.Pro597Leu Single submitter ⚠
p.Pro636Leu Single submitter ⚠
p.Pro652Ser Single submitter ⚠
p.Pro710Leu Single submitter ⚠
p.Pro756Leu Single submitter ⚠
p.Pro852Ser Single submitter ⚠
p.Pro920Ala Single submitter ⚠
p.Pro99Ser Single submitter ⚠
p.Ser1067Leu Single submitter ⚠
p.Ser138Leu Single submitter ⚠
p.Ser1399Phe Single submitter ⚠
p.Ser144Phe Single submitter ⚠
p.Ser161Leu Single submitter ⚠
p.Ser1847Pro Single submitter ⚠
p.Ser1899Thr Single submitter ⚠
p.Ser1917Phe Single submitter ⚠
p.Ser257Ala Single submitter ⚠
p.Ser415Phe Single submitter ⚠
p.Ser425Leu Single submitter ⚠
p.Ser45Phe Single submitter ⚠
p.Ser675Pro Single submitter ⚠
p.Ser747Ile Single submitter ⚠
p.Ser925Arg Single submitter ⚠
p.Thr1039Ile Single submitter ⚠
p.Thr1150Met Single submitter ⚠
p.Thr1247Ile Single submitter ⚠
p.Thr1589Ile Single submitter ⚠
p.Thr174Ile Single submitter ⚠
p.Thr1863Met Single submitter ⚠
p.Thr1910Ser Single submitter ⚠
p.Thr1973Ser Single submitter ⚠
p.Thr214Ala Single submitter ⚠
p.Thr248Ser Single submitter ⚠
p.Thr258Ser Single submitter ⚠
p.Thr350Lys Single submitter ⚠
p.Thr416Ile Single submitter ⚠
p.Thr61Met Single submitter ⚠
p.Thr716Ile Single submitter ⚠
p.Thr725Ile Single submitter ⚠
p.Thr760Arg Single submitter ⚠
p.Thr781Ile Single submitter ⚠
p.Thr788Ile Single submitter ⚠
p.Trp1882Ser Single submitter ⚠
p.Trp309Arg Single submitter ⚠
p.Tyr1342His Single submitter ⚠
p.Tyr175His Single submitter ⚠
p.Tyr1894Cys Single submitter ⚠
p.Val1449Met Single submitter ⚠
p.Val1694Ala Single submitter ⚠
p.Val1850Leu Single submitter ⚠
p.Val1850Met Single submitter ⚠
p.Val1884Ala Single submitter ⚠
p.Val1884Ile Single submitter ⚠
p.Val342Met Single submitter ⚠
p.Val374Met Single submitter ⚠
p.Val512Met Single submitter ⚠
p.Val897Ile Single submitter ⚠
p.Val931Met Single submitter ⚠
p.Arg373Gln No assertion criteria Hirschsprung disease ⚠