HEPHL1 — 238 ClinVar variants

All ClinVar germline HEPHL1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 177 flagged for review →

6 Likely pathogenic · 11 Benign · 1 Benign/Likely benign · 34 Likely benign · 186 Uncertain significance

Full HEPHL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 177

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 lean, ClinVar uncertain 140

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

Predictors split 37

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

All HEPHL1 variants

Likely pathogenic 6

c.2906-1G>C Single submitter pili torti-developmental delay-neurological abnormalities syndrome
p.Arg122Ter Single submitter
p.Arg953Ter Single submitter
p.Pro2fs Single submitter pili torti-developmental delay-neurological abnormalities syndrome
p.Ser137Ter Single submitter pili torti-developmental delay-neurological abnormalities syndrome
p.Tyr215Ter Single submitter pili torti-developmental delay-neurological abnormalities syndrome

Benign 11

c.1232+9C>G Multiple submitters pili torti-developmental delay-neurological abnormalities syndrome
c.3046-35G>T Multiple submitters pili torti-developmental delay-neurological abnormalities syndrome
p.Asn251Asp Multiple submitters pili torti-developmental delay-neurological abnormalities syndrome
p.Phe383= Single submitter
p.Thr1130= Single submitter
p.Arg224Gln No assertion criteria HEPHL1-related disorder
p.Arg432Gln No assertion criteria HEPHL1-related disorder
p.Asp920Glu No assertion criteria HEPHL1-related disorder
p.Leu1137Phe No assertion criteria HEPHL1-related disorder
p.Lys374Asn No assertion criteria HEPHL1-related disorder
p.Ser1076= No assertion criteria HEPHL1-related disorder

Benign/Likely benign 1

p.Phe754= Multiple submitters

Likely benign 34

p.Pro1090= Multiple submitters
p.Pro869= Multiple submitters
c.1504+7C>T Single submitter
c.1504+9C>T Single submitter
c.171-11C>T Single submitter
c.1867+20C>T Single submitter
c.1867+4T>C Single submitter
c.1868-20G>A Single submitter
c.2080+19T>C Single submitter
c.415+18A>T Single submitter
p.Arg381His Single submitter
p.Arg762Gly Single submitter
p.Arg81His Single submitter
p.Asn625= Single submitter
p.Asp191= Single submitter
p.Glu806= Single submitter
p.Gly277= Single submitter
p.His681= Single submitter
p.Ile211Val Single submitter
p.Leu500Val Single submitter
p.Met682Val Single submitter
p.Pro95= Single submitter
p.Thr1064= Single submitter
p.Thr584= Single submitter
p.Tyr481= Single submitter
p.Tyr714= Single submitter
p.Tyr729= Single submitter
p.Val323Ile Single submitter
p.Val555= Single submitter
p.Val823Ile Single submitter
p.Val921Ile Single submitter
p.Arg81Cys No assertion criteria HEPHL1-related disorder
p.Met703Ile No assertion criteria HEPHL1-related disorder
p.Thr175Ile No assertion criteria HEPHL1-related disorder

Uncertain significance 186

p.Arg1021Gly Multiple submitters ⚠
p.Asn990His Multiple submitters ⚠
c.1505-12_1511del Single submitter
p.Ala1057Ser Single submitter ⚠
p.Ala1140Glu Single submitter ⚠
p.Ala1153Asp Single submitter ⚠
p.Ala173Glu Single submitter ⚠
p.Ala179Thr Single submitter ⚠
p.Ala408Thr Single submitter ⚠
p.Ala449Thr Single submitter ⚠
p.Ala493Pro Single submitter ⚠
p.Ala761Ser Single submitter ⚠
p.Ala817Asp Single submitter ⚠
p.Ala926Thr Single submitter ⚠
p.Arg319Trp Single submitter ⚠
p.Arg380Ser Single submitter ⚠
p.Arg3Trp Single submitter ⚠
p.Arg65Lys Single submitter ⚠
p.Arg673Gln Single submitter ⚠
p.Arg722Ser Single submitter ⚠
p.Arg728Leu Single submitter ⚠
p.Arg773Cys Single submitter ⚠
p.Arg773Gly Single submitter ⚠
p.Arg804Leu Single submitter ⚠
p.Arg833Gly Single submitter
p.Arg908Leu Single submitter ⚠
p.Asn1071Ser Single submitter ⚠
p.Asn242Tyr Single submitter ⚠
p.Asn278His Single submitter ⚠
p.Asn407His Single submitter ⚠
p.Asn407Lys Single submitter
p.Asn422Asp Single submitter ⚠
p.Asn567Ser Single submitter ⚠
p.Asn631Lys Single submitter ⚠
p.Asn68Lys Single submitter ⚠
p.Asn749His Single submitter ⚠
p.Asn776Ser Single submitter ⚠
p.Asn880Asp Single submitter ⚠
p.Asn880Ser Single submitter pili torti-developmental delay-neurological abnormalities syndrome ⚠
p.Asp1017Gly Single submitter pili torti-developmental delay-neurological abnormalities syndrome ⚠
p.Asp1026Gly Single submitter ⚠
p.Asp221Tyr Single submitter ⚠
p.Asp234His Single submitter ⚠
p.Asp478Asn Single submitter ⚠
p.Asp491Glu Single submitter ⚠
p.Asp495Val Single submitter ⚠
p.Asp569Glu Single submitter ⚠
p.Asp595Asn Single submitter ⚠
p.Asp609Glu Single submitter ⚠
p.Asp745Val Single submitter ⚠
p.Gln1150Pro Single submitter ⚠
p.Gln419His Single submitter ⚠
p.Gln419Pro Single submitter ⚠
p.Gln712His Single submitter
p.Glu171Lys Single submitter ⚠
p.Glu338Lys Single submitter ⚠
p.Glu435Gln Single submitter ⚠
p.Glu435Gly Single submitter ⚠
p.Glu450Asp Single submitter ⚠
p.Glu514Lys Single submitter ⚠
p.Glu809Asp Single submitter ⚠
p.Glu963Asp Single submitter ⚠
p.Gly1081Arg Single submitter ⚠
p.Gly1104Asp Single submitter ⚠
p.Gly148Ala Single submitter ⚠
p.Gly397Ser Single submitter ⚠
p.Gly466Ser Single submitter ⚠
p.Gly658Arg Single submitter ⚠
p.Gly711Ser Single submitter ⚠
p.Gly980Cys Single submitter ⚠
p.His1085Arg Single submitter ⚠
p.His127Pro Single submitter ⚠
p.His318Arg Single submitter ⚠
p.His453Tyr Single submitter ⚠
p.His672Arg Single submitter ⚠
p.His692Arg Single submitter ⚠
p.His705Arg Single submitter ⚠
p.Ile103Thr Single submitter ⚠
p.Ile1073Thr Single submitter ⚠
p.Ile1121Val Single submitter ⚠
p.Ile1122Thr Single submitter ⚠
p.Ile190Phe Single submitter ⚠
p.Ile306Val Single submitter ⚠
p.Ile31Val Single submitter ⚠
p.Ile424Thr Single submitter ⚠
p.Ile575Thr Single submitter ⚠
p.Ile659Thr Single submitter ⚠
p.Ile666Thr Single submitter ⚠
p.Ile737Asn Single submitter ⚠
p.Ile73Met Single submitter ⚠
p.Leu100Arg Single submitter ⚠
p.Leu1127Ile Single submitter ⚠
p.Leu1135Ile Single submitter ⚠
p.Leu331Phe Single submitter ⚠
p.Leu390Ile Single submitter ⚠
p.Leu406Arg Single submitter ⚠
p.Leu447Val Single submitter ⚠
p.Leu63Phe Single submitter
p.Lys1015Glu Single submitter ⚠
p.Lys45Glu Single submitter ⚠
p.Lys76Asn Single submitter ⚠
p.Lys946Asn Single submitter ⚠
p.Lys973Thr Single submitter ⚠
p.Met1059Thr Single submitter pili torti-developmental delay-neurological abnormalities syndrome ⚠
p.Met284Ile Single submitter ⚠
p.Met284Thr Single submitter ⚠
p.Met656Ile Single submitter
p.Met656Thr Single submitter ⚠
p.Met731Ile Single submitter ⚠
p.Met814Val Single submitter ⚠
p.Met845Ile Single submitter ⚠
p.Met855Ile Single submitter ⚠
p.Met855Lys Single submitter ⚠
p.Phe1032Leu Single submitter ⚠
p.Phe1103Ser Single submitter ⚠
p.Phe15Ser Single submitter ⚠
p.Phe594Val Single submitter ⚠
p.Phe615Ser Single submitter ⚠
p.Phe754Leu Single submitter ⚠
p.Phe961Ser Single submitter ⚠
p.Pro1029Ser Single submitter ⚠
p.Pro1042Ser Single submitter ⚠
p.Pro1090Leu Single submitter ⚠
p.Pro340Thr Single submitter ⚠
p.Pro42Ser Single submitter ⚠
p.Pro528Ala Single submitter ⚠
p.Pro605Ser Single submitter ⚠
p.Pro633Arg Single submitter ⚠
p.Pro724Ala Single submitter ⚠
p.Pro748Ala Single submitter pili torti-developmental delay-neurological abnormalities syndrome ⚠
p.Pro854Ser Single submitter ⚠
p.Ser1076Pro Single submitter ⚠
p.Ser1134Cys Single submitter ⚠
p.Ser125Cys Single submitter ⚠
p.Ser238Thr Single submitter ⚠
p.Ser291Phe Single submitter ⚠
p.Ser618Phe Single submitter ⚠
p.Ser675Pro Single submitter ⚠
p.Ser72Asn Single submitter ⚠
p.Ser872Thr Single submitter ⚠
p.Ser872Tyr Single submitter ⚠
p.Ser919Arg Single submitter ⚠
p.Ser964Arg Single submitter ⚠
p.Ser998Asn Single submitter ⚠
p.Thr1062Ser Single submitter ⚠
p.Thr1130Met Single submitter ⚠
p.Thr1144Ala Single submitter ⚠
p.Thr163Ala Single submitter ⚠
p.Thr218Ile Single submitter ⚠
p.Thr312Asn Single submitter ⚠
p.Thr333Ala Single submitter ⚠
p.Thr517Ala Single submitter ⚠
p.Thr774Ile Single submitter
p.Thr86Ile Single submitter ⚠
p.Thr958Ile Single submitter ⚠
p.Trp239Arg Single submitter ⚠
p.Trp38Cys Single submitter ⚠
p.Trp603Ter Single submitter
p.Trp96Ser Single submitter ⚠
p.Tyr1020Cys Single submitter ⚠
p.Tyr1020His Single submitter ⚠
p.Tyr1025Cys Single submitter ⚠
p.Tyr1101His Single submitter ⚠
p.Tyr133Cys Single submitter ⚠
p.Tyr164Asp Single submitter ⚠
p.Tyr29Cys Single submitter ⚠
p.Tyr428Cys Single submitter ⚠
p.Tyr714His Single submitter ⚠
p.Tyr736His Single submitter ⚠
p.Tyr787Cys Single submitter ⚠
p.Tyr939Cys Single submitter ⚠
p.Tyr947His Single submitter ⚠
p.Val1051Leu Single submitter ⚠
p.Val131Ile Single submitter ⚠
p.Val34Leu Single submitter ⚠
p.Val41Ala Single submitter ⚠
p.Val41Ile Single submitter ⚠
p.Val488Met Single submitter ⚠
p.Val526Ile Single submitter ⚠
p.Val565Ile Single submitter ⚠
p.Val742Ala Single submitter ⚠
p.Val759Gly Single submitter ⚠
p.Val786Ala Single submitter ⚠
p.Val885Phe Single submitter ⚠
p.Val921Ala Single submitter ⚠
p.Arg1094Ter No assertion criteria lichen planopilaris