HELZ — 209 ClinVar variants

All ClinVar germline HELZ variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 190 flagged for review →

1 Likely pathogenic · 10 Likely benign · 198 Uncertain significance

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

⚑ Evidence disagreements 190

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.

HELZ p.Ile1108Val Likely pathogenic Single submitter
Abnormal brain morphology

Predictors lean, ClinVar uncertain 145

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 44

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

All HELZ variants

Likely pathogenic 1

p.Ile1108Val Single submitter Abnormal brain morphology ⚠

Likely benign 10

p.Ala1530Thr Single submitter
p.Asn1880Ser Single submitter
p.Gln1453Pro Single submitter
p.Ile1483Thr Single submitter
p.Ile1724Val Single submitter
p.Ile414Val Single submitter
p.Pro1304Ser Single submitter
p.Pro627= Single submitter
p.Ser1519Asn Single submitter
p.Val1774Ala Single submitter

Uncertain significance 198

p.Arg1652His Multiple submitters ⚠
c.*4461C>T Single submitter pervasive developmental disorder
p.Ala1161Pro Single submitter
p.Ala1351Thr Single submitter ⚠
p.Ala1430Asp Single submitter
p.Ala1437Val Single submitter ⚠
p.Ala1467Thr Single submitter ⚠
p.Ala1504Thr Single submitter ⚠
p.Ala1723Gly Single submitter ⚠
p.Ala1876Thr Single submitter ⚠
p.Ala1888Val Single submitter ⚠
p.Ala1902Thr Single submitter ⚠
p.Ala209Thr Single submitter ⚠
p.Ala209Val Single submitter ⚠
p.Ala523Val Single submitter ⚠
p.Ala606Val Single submitter ⚠
p.Ala717Gly Single submitter ⚠
p.Ala750Thr Single submitter ⚠
p.Ala809Pro Single submitter ⚠
p.Arg1219Gly Single submitter ⚠
p.Arg1439Trp Single submitter ⚠
p.Arg1498His Single submitter ⚠
p.Arg1498Ser Single submitter ⚠
p.Arg1514Gln Single submitter ⚠
p.Arg1514Trp Single submitter ⚠
p.Arg1592Gln Single submitter ⚠
p.Arg1592Trp Single submitter ⚠
p.Arg1755Gln Single submitter ⚠
p.Arg1760Lys Single submitter ⚠
p.Arg378Gly Single submitter ⚠
p.Arg405Cys Single submitter ⚠
p.Arg405His Single submitter ⚠
p.Arg405Leu Single submitter ⚠
p.Arg510His Single submitter ⚠
p.Arg54His Single submitter ⚠
p.Arg582Gln Single submitter ⚠
p.Arg582Trp Single submitter ⚠
p.Arg597Gln Single submitter ⚠
p.Arg766Gln Single submitter ⚠
p.Arg906Gln Single submitter ⚠
p.Arg96Trp Single submitter ⚠
p.Asn1138Lys Single submitter ⚠
p.Asn1236Asp Single submitter ⚠
p.Asn1338Ser Single submitter ⚠
p.Asn1357Lys Single submitter ⚠
p.Asn1385Ser Single submitter ⚠
p.Asn1392Ser Single submitter ⚠
p.Asn1409His Single submitter ⚠
p.Asn1428Thr Single submitter ⚠
p.Asn1633Asp Single submitter ⚠
p.Asn1635His Single submitter ⚠
p.Asn1635Ser Single submitter ⚠
p.Asn1797Ser Single submitter ⚠
p.Asn226Asp Single submitter ⚠
p.Asn265Ser Single submitter ⚠
p.Asn920Lys Single submitter ⚠
p.Asp1185Val Single submitter ⚠
p.Asp1636Gly Single submitter ⚠
p.Asp21Asn Single submitter ⚠
p.Asp21Glu Single submitter ⚠
p.Cys601Tyr Single submitter ⚠
p.Cys779Tyr Single submitter ⚠
p.Cys863Tyr Single submitter ⚠
p.Gln1084Glu Single submitter ⚠
p.Gln1148Arg Single submitter
p.Gln1263Arg Single submitter ⚠
p.Gln1276His Single submitter ⚠
p.Gln1376Arg Single submitter ⚠
p.Gln1400Arg Single submitter ⚠
p.Gln1405Lys Single submitter ⚠
p.Gln1512His Single submitter ⚠
p.Gln1793Lys Single submitter ⚠
p.Gln1874Glu Single submitter ⚠
p.Gln637His Single submitter ⚠
p.Glu1013Asp Single submitter ⚠
p.Glu1582Asp Single submitter ⚠
p.Glu1582Gly Single submitter
p.Glu1747Lys Single submitter
p.Glu331Asp Single submitter ⚠
p.Glu390Lys Single submitter ⚠
p.Glu519Ala Single submitter ⚠
p.Glu556Lys Single submitter ⚠
p.Gly1528Ser Single submitter ⚠
p.Gly152Glu Single submitter ⚠
p.Gly1549Glu Single submitter ⚠
p.Gly1929Arg Single submitter ⚠
p.His1004Gln Single submitter ⚠
p.His1171Tyr Single submitter ⚠
p.His1268Gln Single submitter ⚠
p.His1341Pro Single submitter ⚠
p.His1350Asn Single submitter ⚠
p.His1350Tyr Single submitter ⚠
p.His1521Asn Single submitter ⚠
p.His1536Gln Single submitter ⚠
p.His1542Arg Single submitter ⚠
p.His1551Tyr Single submitter ⚠
p.His1585Arg Single submitter ⚠
p.His167Tyr Single submitter ⚠
p.His461Gln Single submitter ⚠
p.His684Arg Single submitter ⚠
p.His742Pro Single submitter ⚠
p.His851Arg Single submitter ⚠
p.Ile1155Thr Single submitter ⚠
p.Ile1159Val Single submitter ⚠
p.Ile1261Met Single submitter ⚠
p.Ile1373Val Single submitter ⚠
p.Ile1641Thr Single submitter ⚠
p.Ile1717Val Single submitter ⚠
p.Ile620Met Single submitter ⚠
p.Ile620Val Single submitter ⚠
p.Ile653Val Single submitter ⚠
p.Leu124Val Single submitter ⚠
p.Leu1363Phe Single submitter ⚠
p.Leu150Phe Single submitter ⚠
p.Leu1561Pro Single submitter ⚠
p.Leu1669Val Single submitter ⚠
p.Leu1732Ser Single submitter ⚠
p.Leu428Val Single submitter ⚠
p.Leu460Val Single submitter
p.Leu900Val Single submitter ⚠
p.Lys1129Glu Single submitter ⚠
p.Lys1835Glu Single submitter ⚠
p.Lys1838Arg Single submitter ⚠
p.Lys251Glu Single submitter ⚠
p.Lys530Glu Single submitter ⚠
p.Lys986Arg Single submitter
p.Met102Thr Single submitter ⚠
p.Met236Val Single submitter ⚠
p.Met337Leu Single submitter ⚠
p.Met376Thr Single submitter ⚠
p.Met603Leu Single submitter ⚠
p.Met800Thr Single submitter ⚠
p.Met806Ile Single submitter ⚠
p.Phe1923Leu Single submitter ⚠
p.Phe593Leu Single submitter ⚠
p.Pro1167Ala Single submitter ⚠
p.Pro1167Arg Single submitter
p.Pro1167Thr Single submitter ⚠
p.Pro1210Arg Single submitter ⚠
p.Pro1356Ser Single submitter ⚠
p.Pro1362Leu Single submitter ⚠
p.Pro1364Leu Single submitter ⚠
p.Pro1395Leu Single submitter ⚠
p.Pro1396Thr Single submitter ⚠
p.Pro1415Leu Single submitter ⚠
p.Pro1450Leu Single submitter ⚠
p.Pro1456Ser Single submitter ⚠
p.Pro1473Ser Single submitter ⚠
p.Pro1487Thr Single submitter ⚠
p.Pro1533Ala Single submitter ⚠
p.Pro1546Leu Single submitter ⚠
p.Pro1553Leu Single submitter ⚠
p.Pro1619Ser Single submitter ⚠
p.Pro1622Ala Single submitter ⚠
p.Pro1713Ala Single submitter ⚠
p.Pro1731Ser Single submitter ⚠
p.Pro1812Ala Single submitter ⚠
p.Pro1817Leu Single submitter ⚠
p.Pro1909Leu Single submitter ⚠
p.Pro599Ser Single submitter ⚠
p.Pro662Leu Single submitter ⚠
p.Pro663Ser Single submitter ⚠
p.Pro720Thr Single submitter ⚠
p.Pro857Ala Single submitter ⚠
p.Ser1056Tyr Single submitter ⚠
p.Ser1328Arg Single submitter ⚠
p.Ser1502Asn Single submitter ⚠
p.Ser1529Asn Single submitter ⚠
p.Ser1589Thr Single submitter ⚠
p.Ser1614Gly Single submitter ⚠
p.Ser1809Pro Single submitter ⚠
p.Ser1846Leu Single submitter ⚠
p.Ser450Thr Single submitter ⚠
p.Ser476Ile Single submitter ⚠
p.Ser888Arg Single submitter ⚠
p.Ser915Cys Single submitter ⚠
p.Thr1007Ile Single submitter ⚠
p.Thr1120Asn Single submitter ⚠
p.Thr1302Ala Single submitter ⚠
p.Thr1736Ala Single submitter ⚠
p.Tyr1025Cys Single submitter ⚠
p.Tyr1098His Single submitter ⚠
p.Tyr1199Cys Single submitter ⚠
p.Tyr1573Ser Single submitter ⚠
p.Tyr1748His Single submitter ⚠
p.Tyr535Cys Single submitter ⚠
p.Tyr670Cys Single submitter ⚠
p.Tyr706Cys Single submitter ⚠
p.Tyr875Cys Single submitter ⚠
p.Val1181Gly Single submitter ⚠
p.Val1324Gly Single submitter ⚠
p.Val1448Ile Single submitter ⚠
p.Val1555Ala Single submitter ⚠
p.Val1643Leu Single submitter ⚠
p.Val1859Ala Single submitter ⚠
p.Val539Leu Single submitter ⚠
p.Val842Ile Single submitter ⚠
p.Val953Ala Single submitter ⚠