ROS1 — 337 ClinVar variants

All ClinVar germline ROS1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 250 flagged for review →

3 Pathogenic · 2 Likely pathogenic · 3 Conflicting · 40 Benign · 4 Benign/Likely benign · 33 Likely benign · 252 Uncertain significance

Full ROS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 250

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 3

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

ROS1 p.Arg2120Gln Conflicting Single submitter
ROS1 p.Asn1090Ile Conflicting Single submitter
ROS1 p.Gly374Ala Conflicting Single submitter
Abnormal brain morphology

Predictors lean, ClinVar uncertain 208

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 208

Predictors split 39

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

All ROS1 variants

Pathogenic 3

p.Gly1130Arg Single submitter lung adenocarcinoma ⚠
p.Asn1528fs No assertion criteria Short stature
p.Gly2026Arg No assertion criteria lung adenocarcinoma

Likely pathogenic 2

p.Ile1864fs Single submitter Male infertility with azoospermia or oligozoospermia due to single gene mutation
p.Leu1204Ter Single submitter Male infertility with azoospermia or oligozoospermia due to single gene mutation

Conflicting classifications of pathogenicity 3

p.Arg2120Gln Single submitter ⚠
p.Asn1090Ile Single submitter ⚠
p.Gly374Ala Single submitter Abnormal brain morphology ⚠

Benign 40

p.Arg1500Gly Multiple submitters
p.Asp1770His Multiple submitters
p.Glu1896Lys Multiple submitters
p.Thr1467= Multiple submitters
c.1191+8C>T Single submitter
c.2583-3C>T Single submitter
c.3430+42C>T Single submitter lung adenocarcinoma
c.3840-5T>C Single submitter
c.5348+9G>A Single submitter
c.5349-5dup Single submitter
c.5540-26T>A Single submitter
c.5623+1427_5623+1429dup Single submitter
c.5759+4T>G Single submitter
c.5760-265G>T Single submitter
c.5923-4A>G Single submitter
c.883+3A>G Single submitter
c.883+8dup Single submitter
p.Ala1125= Single submitter
p.Ala1908= Single submitter
p.Arg176Gln Single submitter
p.Arg2077= Single submitter
p.Asn2234Lys Single submitter
p.Asn785Ser Single submitter
p.Asp2207Asn Single submitter
p.Asp613Gly Single submitter
p.Glu657= Single submitter
p.Leu1589= Single submitter
p.Lys1021Met Single submitter
p.Lys2222Gln Single submitter
p.Lys2322Arg Single submitter
p.Lys470Glu Single submitter
p.Met787Ile Single submitter
p.Phe937Leu Single submitter
p.Pro1653Thr Single submitter
p.Pro233Ser Single submitter
p.Ser1104Leu Single submitter
p.Ser2223Cys Single submitter
p.Ser668= Single submitter
p.Thr1172= Single submitter
p.Thr717= Single submitter

Benign/Likely benign 4

p.Leu1331= Multiple submitters
p.Ser1298= Multiple submitters
p.Ser88= Multiple submitters
p.Val222= Multiple submitters

Likely benign 33

c.4126+3A>G Multiple submitters
p.Gly1022Asp Multiple submitters ⚠
p.Leu755Ile Multiple submitters
p.Ser648Phe Multiple submitters
p.Thr799Asn Multiple submitters
p.Ala1181= Single submitter
p.Ala2123= Single submitter
p.Ala599= Single submitter
p.Arg451Gln Single submitter
p.Asn1930Ser Single submitter
p.Asp2207Glu Single submitter
p.Glu1692= Single submitter
p.Ile1570Val Single submitter
p.Ile2252Val Single submitter
p.Ile383Val Single submitter
p.Ile469Val Single submitter
p.Leu20= Single submitter
p.Lys1884Glu Single submitter
p.Phe1433Ser Single submitter
p.Phe2216Ser Single submitter
p.Pro1345= Single submitter
p.Pro1656= Single submitter
p.Pro9Leu Single submitter
p.Ser2082= Single submitter
p.Thr1225= Single submitter
p.Thr1734= Single submitter
p.Thr926= Single submitter
p.Trp151Arg Single submitter ⚠
p.Val1182Ile Single submitter
p.Val1555= Single submitter
p.Met394Thr No assertion criteria ROS1-related disorder ⚠
p.Pro932= No assertion criteria ROS1-related disorder
p.Ser379Pro No assertion criteria ROS1-related disorder

Uncertain significance 252

c.3366+23T>C Single submitter squamous cell carcinoma
c.5062-46A>C Single submitter lung adenocarcinoma
p.Ala1175Gly Single submitter ⚠
p.Ala131Thr Single submitter ⚠
p.Ala1417Thr Single submitter ⚠
p.Ala1442Val Single submitter ⚠
p.Ala1453Val Single submitter ⚠
p.Ala1827Glu Single submitter ⚠
p.Ala1908Thr Single submitter ⚠
p.Ala2100Ser Single submitter
p.Ala329Thr Single submitter ⚠
p.Ala419Thr Single submitter ⚠
p.Ala468Ser Single submitter ⚠
p.Ala592Ser Single submitter ⚠
p.Ala646Ser Single submitter ⚠
p.Arg1043Ser Single submitter ⚠
p.Arg1177Ser Single submitter ⚠
p.Arg1281Cys Single submitter ⚠
p.Arg1281His Single submitter ⚠
p.Arg1281Ser Single submitter ⚠
p.Arg1603Lys Single submitter ⚠
p.Arg1611Ser Single submitter ⚠
p.Arg1722Lys Single submitter ⚠
p.Arg2036Trp Single submitter ⚠
p.Arg2199Ile Single submitter ⚠
p.Arg326Trp Single submitter ⚠
p.Arg451Trp Single submitter ⚠
p.Arg457Cys Single submitter ⚠
p.Arg858Gln Single submitter ⚠
p.Arg889Trp Single submitter ⚠
p.Asn1056Ser Single submitter lung adenocarcinoma ⚠
p.Asn1090Tyr Single submitter ⚠
p.Asn1100His Single submitter ⚠
p.Asn1206Asp Single submitter ⚠
p.Asn123Thr Single submitter ⚠
p.Asn132Asp Single submitter ⚠
p.Asn1549Thr Single submitter ⚠
p.Asn1677Ser Single submitter ⚠
p.Asn1691Lys Single submitter ⚠
p.Asn211His Single submitter ⚠
p.Asn2214Ile Single submitter ⚠
p.Asn2229Ser Single submitter ⚠
p.Asn2262Ser Single submitter ⚠
p.Asn535Ser Single submitter ⚠
p.Asn623Thr Single submitter ⚠
p.Asn630His Single submitter ⚠
p.Asn785Lys Single submitter ⚠
p.Asp1227Gly Single submitter ⚠
p.Asp1385Val Single submitter ⚠
p.Asp1435Gly Single submitter ⚠
p.Asp1444Gly Single submitter ⚠
p.Asp1532Glu Single submitter ⚠
p.Asp2027Glu Single submitter ⚠
p.Asp2243Glu Single submitter ⚠
p.Asp2251Gly Single submitter ⚠
p.Asp2306Gly Single submitter ⚠
p.Asp2338Asn Single submitter ⚠
p.Asp340Val Single submitter ⚠
p.Asp530Val Single submitter
p.Asp971Ala Single submitter ⚠
p.Cys1052Arg Single submitter ⚠
p.Cys1632Tyr Single submitter ⚠
p.Cys1773Arg Single submitter ⚠
p.Cys1809Ser Single submitter ⚠
p.Cys19Tyr Single submitter ⚠
p.Cys2079Tyr Single submitter ⚠
p.Cys76Arg Single submitter ⚠
p.Cys89Arg Single submitter ⚠
p.Cys89Trp Single submitter ⚠
p.Gln1523Arg Single submitter ⚠
p.Gln1702Leu Single submitter ⚠
p.Gln1764Glu Single submitter ⚠
p.Gln1983His Single submitter ⚠
p.Gln2210His Single submitter ⚠
p.Gln2277Arg Single submitter ⚠
p.Gln228Glu Single submitter lung adenocarcinoma ⚠
p.Gln2314His Single submitter ⚠
p.Gln246His Single submitter ⚠
p.Gln246Lys Single submitter ⚠
p.Gln860Arg Single submitter ⚠
p.Glu1260Gln Single submitter ⚠
p.Glu1599Asp Single submitter ⚠
p.Glu1987Ala Single submitter ⚠
p.Glu213Lys Single submitter ⚠
p.Glu221Gly Single submitter ⚠
p.Glu2240Lys Single submitter ⚠
p.Glu2312Lys Single submitter ⚠
p.Glu299Gln Single submitter ⚠
p.Glu87Gln Single submitter ⚠
p.Gly1196Arg Single submitter ⚠
p.Gly1291Cys Single submitter ⚠
p.Gly1965Arg Single submitter ⚠
p.Gly2335Arg Single submitter ⚠
p.Gly251Ala Single submitter ⚠
p.Gly752Arg Single submitter ⚠
p.Gly905Asp Single submitter ⚠
p.His1633Gln Single submitter ⚠
p.His1695Asp Single submitter ⚠
p.His1877Arg Single submitter ⚠
p.His1920Tyr Single submitter ⚠
p.His2000Arg Single submitter ⚠
p.His323Arg Single submitter ⚠
p.His332Arg Single submitter ⚠
p.His332Asn Single submitter ⚠
p.His497Arg Single submitter ⚠
p.His62Gln Single submitter ⚠
p.His773Leu Single submitter ⚠
p.Ile1083Thr Single submitter ⚠
p.Ile1159Val Single submitter ⚠
p.Ile119Thr Single submitter ⚠
p.Ile1570Thr Single submitter ⚠
p.Ile1819Met Single submitter ⚠
p.Ile1819Val Single submitter ⚠
p.Ile1857Val Single submitter ⚠
p.Ile212Val Single submitter ⚠
p.Ile242Asn Single submitter ⚠
p.Ile272Val Single submitter ⚠
p.Ile378Val Single submitter ⚠
p.Ile423Thr Single submitter ⚠
p.Ile624Thr Single submitter ⚠
p.Ile904Thr Single submitter ⚠
p.Ile953Val Single submitter ⚠
p.Leu1155Arg Single submitter ⚠
p.Leu1282Val Single submitter ⚠
p.Leu1304Val Single submitter ⚠
p.Leu1388Pro Single submitter ⚠
p.Leu1469Ile Single submitter ⚠
p.Leu1557Phe Single submitter ⚠
p.Leu47Phe Single submitter ⚠
p.Leu554Ser Single submitter ⚠
p.Leu573Val Single submitter ⚠
p.Leu726Met Single submitter ⚠
p.Leu770Val Single submitter ⚠
p.Leu809Val Single submitter
p.Leu883Arg Single submitter ⚠
p.Leu988Val Single submitter ⚠
p.Lys1055Glu Single submitter ⚠
p.Lys165Gln Single submitter ⚠
p.Lys1697Glu Single submitter ⚠
p.Lys1812Glu Single submitter ⚠
p.Lys35Asn Single submitter ⚠
p.Lys524Asn Single submitter ⚠
p.Met1190Thr Single submitter ⚠
p.Met1294Ile Single submitter ⚠
p.Met1430Ile Single submitter ⚠
p.Met2122Ile Single submitter ⚠
p.Met2122Lys Single submitter ⚠
p.Met2258Thr Single submitter ⚠
p.Met487Thr Single submitter ⚠
p.Met705Thr Single submitter ⚠
p.Met884Ile Single submitter ⚠
p.Phe1108Leu Single submitter ⚠
p.Phe1121Ser Single submitter ⚠
p.Phe1801Leu Single submitter ⚠
p.Phe935Ser Single submitter ⚠
p.Pro1005Arg Single submitter
p.Pro1005Thr Single submitter ⚠
p.Pro1036Arg Single submitter ⚠
p.Pro1103Leu Single submitter ⚠
p.Pro1310Thr Single submitter ⚠
p.Pro1372Arg Single submitter ⚠
p.Pro1372Ser Single submitter ⚠
p.Pro1432Arg Single submitter ⚠
p.Pro1516Gln Single submitter ⚠
p.Pro1538Thr Single submitter ⚠
p.Pro1644Leu Single submitter ⚠
p.Pro1737Ala Single submitter ⚠
p.Pro2015Thr Single submitter ⚠
p.Pro2157Arg Single submitter ⚠
p.Pro2323Ala Single submitter ⚠
p.Pro2323Thr Single submitter ⚠
p.Pro685Thr Single submitter ⚠
p.Pro691Ala Single submitter ⚠
p.Pro996Thr Single submitter ⚠
p.Ser1049Gly Single submitter ⚠
p.Ser1087Asn Single submitter ⚠
p.Ser134Phe Single submitter ⚠
p.Ser1398Ile Single submitter ⚠
p.Ser1420Arg Single submitter ⚠
p.Ser1420Asn Single submitter ⚠
p.Ser1518Leu Single submitter ⚠
p.Ser1564Pro Single submitter ⚠
p.Ser1620Phe Single submitter ⚠
p.Ser1733Arg Single submitter ⚠
p.Ser1733Asn Single submitter ⚠
p.Ser1739Thr Single submitter ⚠
p.Ser1759Thr Single submitter ⚠
p.Ser214Arg Single submitter ⚠
p.Ser261Ala Single submitter ⚠
p.Ser292Phe Single submitter ⚠
p.Ser309Pro Single submitter ⚠
p.Ser559Leu Single submitter ⚠
p.Ser579Phe Single submitter ⚠
p.Ser598Ala Single submitter ⚠
p.Ser625Asn Single submitter ⚠
p.Ser647Asn Single submitter ⚠
p.Ser739Arg Single submitter ⚠
p.Ser879Cys Single submitter ⚠
p.Ser927Phe Single submitter ⚠
p.Ser936Pro Single submitter ⚠
p.Thr1142Ile Single submitter ⚠
p.Thr1339Asn Single submitter ⚠
p.Thr1399Ala Single submitter ⚠
p.Thr1519Lys Single submitter ⚠
p.Thr1664Ala Single submitter ⚠
p.Thr16Pro Single submitter ⚠
p.Thr1742Lys Single submitter ⚠
p.Thr1776Pro Single submitter ⚠
p.Thr1981Ile Single submitter ⚠
p.Thr2046Asn Single submitter ⚠
p.Thr252Arg Single submitter ⚠
p.Thr308Ile Single submitter ⚠
p.Thr618Ser Single submitter ⚠
p.Thr771Met Single submitter ⚠
p.Thr807Ala Single submitter ⚠
p.Thr832Asn Single submitter ⚠
p.Thr926Ile Single submitter ⚠
p.Trp1019Cys Single submitter ⚠
p.Trp21Arg Single submitter ⚠
p.Trp892Arg Single submitter ⚠
p.Tyr1283Cys Single submitter ⚠
p.Tyr1402Asn Single submitter ⚠
p.Tyr1520His Single submitter ⚠
p.Tyr1530His Single submitter
p.Tyr162Cys Single submitter ⚠
p.Tyr2041Cys Single submitter ⚠
p.Tyr260Cys Single submitter ⚠
p.Tyr714Cys Single submitter ⚠
p.Tyr841Cys Single submitter ⚠
p.Tyr886Phe Single submitter ⚠
p.Tyr977His Single submitter ⚠
p.Val1060Ala Single submitter ⚠
p.Val1249Ala Single submitter ⚠
p.Val1488Ile Single submitter ⚠
p.Val1629Phe Single submitter
p.Val1696Ala Single submitter ⚠
p.Val1964Asp Single submitter ⚠
p.Val1971Ala Single submitter ⚠
p.Val2048Ile Single submitter ⚠
p.Val295Ala Single submitter ⚠
p.Val346Ile Single submitter ⚠
p.Val432Phe Single submitter ⚠
p.Val555Asp Single submitter
p.Val575Met Single submitter ⚠
p.Val777Phe Single submitter ⚠
p.Val792Ala Single submitter ⚠
p.Val941Ile Single submitter ⚠
p.Asp2027Asn No assertion criteria lung sarcomatoid carcinoma ⚠
p.Glu2226Lys No assertion criteria ⚠
p.Gly1333Glu No assertion criteria ROS1-related disorder ⚠
p.Gly236Ser No assertion criteria ⚠
p.Thr1025Ala No assertion criteria Short stature ⚠