Sugi Variant

Sugi Variant/KNL1

KNL1 — 421 ClinVar variants

All ClinVar germline KNL1 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 162 flagged for review →

5 Pathogenic · 18 Likely pathogenic · 31 Conflicting · 50 Benign · 19 Benign/Likely benign · 115 Likely benign · 183 Uncertain significance

Full KNL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 162

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 3

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

Predictors agree, ClinVar conflicts 14

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

Predicted LoF vs a conflicting call 1

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 131

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

Predictors split 13

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

All KNL1 variants

Pathogenic 5

  • p.Asn1565fs Single submitter Inborn genetic diseases
  • p.Gln604Ter Single submitter
  • p.Gly359fs Single submitter microcephaly 4, primary, autosomal recessive
  • p.Ile1729fs Single submitter microcephaly 4, primary, autosomal recessive
  • p.Met2015Ile Single submitter microcephaly 4, primary, autosomal recessive ⚠

Likely pathogenic 18

Conflicting classifications of pathogenicity 31

  • c.250+2T>C Single submitter CASC5 & KNL1-related disorders ⚠
  • c.251-7T>A Single submitter
  • c.251-9T>C Single submitter
  • c.6416-13T>G Single submitter microcephaly 4, primary, autosomal recessive
  • c.6594+10G>A Single submitter microcephaly 4, primary, autosomal recessive
  • c.75+6A>G Single submitter microcephaly 4, primary, autosomal recessive
  • p.Ala1212Thr Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Ala1992Ser Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Ala590Ser Single submitter Inborn genetic diseases ⚠
  • p.Asn1591Ser Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Asn1704= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Asp2161Gly Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Cys1333= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Cys1757= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Glu1846= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Gly1411Arg Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Gly1540Glu Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Ile1191Met Single submitter Inborn genetic diseases ⚠
  • p.Ile1211= Single submitter
  • p.Ile1460Thr Single submitter ⚠
  • p.Leu166Ser Single submitter ⚠
  • p.Leu1877= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Met2015Leu Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Met939Leu Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Pro1688= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Pro248= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Ser756= Single submitter
  • p.Thr1869= Single submitter microcephaly 4, primary, autosomal recessive
  • p.Thr271Ser Single submitter microcephaly 4, primary, autosomal recessive ⚠
  • p.Val2112Ile Single submitter Inborn genetic diseases ⚠
  • p.Val771Ile Single submitter ⚠

Benign 50

Benign/Likely benign 19

Likely benign 115

Uncertain significance 183