Sugi Variant

Sugi Variant/IARS2

IARS2 — 615 ClinVar variants

All ClinVar germline IARS2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 244 flagged for review →

13 Pathogenic · 4 Pathogenic/Likely pathogenic · 12 Likely pathogenic · 14 Conflicting · 45 Benign · 21 Benign/Likely benign · 235 Likely benign · 271 Uncertain significance

Full IARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 244

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 10

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

Predictors lean, ClinVar uncertain 181

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 181

Predictors split 50

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

All IARS2 variants

Pathogenic 13

  • p.Cys110Ter Single submitter
  • p.Gln920Ter Single submitter
  • p.Glu577fs Single submitter
  • p.Glu688Ter Single submitter
  • p.Gly682fs Single submitter Inborn genetic diseases
  • p.His140fs Single submitter
  • p.Ser926fs Single submitter
  • p.Ser94fs Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Tyr97fs Single submitter
  • p.Val105fs Single submitter
  • p.His761Arg No assertion criteria cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome ⚠
  • p.Phe227Ser No assertion criteria cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Pro909Ser No assertion criteria cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome ⚠

Pathogenic/Likely pathogenic 4

  • p.Arg817His Multiple submitters cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome ⚠
  • p.Lys183fs Multiple submitters Leigh syndrome
  • p.Lys649delinsIleTer Multiple submitters cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Tyr117Ter Multiple submitters Leigh syndrome

Likely pathogenic 12

  • c.1066+1G>T Single submitter
  • c.267+2T>A Single submitter
  • c.750-1G>A Single submitter
  • c.860-1G>A Single submitter
  • p.Arg19Ter Single submitter
  • p.Arg784Trp Single submitter ⚠
  • p.Arg816Ter Single submitter
  • p.Gln448Ter Single submitter
  • p.Glu772fs Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Gly874Arg Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome ⚠
  • p.Pro592fs Single submitter
  • p.Trp297Ter Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome

Conflicting classifications of pathogenicity 14

  • p.Ala172Gly Single submitter Inborn genetic diseases ⚠
  • p.Arg267His Single submitter ⚠
  • p.Arg787Gln Single submitter ⚠
  • p.Asp751Asn Single submitter Inborn genetic diseases ⚠
  • p.Glu708Lys Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Gly403Ser Single submitter Inborn genetic diseases ⚠
  • p.Leu329Pro Single submitter ⚠
  • p.Lys317= Single submitter Inborn genetic diseases
  • p.Met1Leu Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Pro909Leu Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome ⚠
  • p.Thr343Ala Single submitter Inborn genetic diseases ⚠
  • p.Thr353Ser Single submitter ⚠
  • p.Trp607Ter Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome
  • p.Val331Ile Single submitter cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome ⚠

Benign 45

Benign/Likely benign 21

Likely benign 235

Uncertain significance 271