Sugi Variant

Sugi Variant/POLR2A

POLR2A — 540 ClinVar variants

All ClinVar germline POLR2A variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 301 flagged for review →

6 Pathogenic · 5 Pathogenic/Likely pathogenic · 29 Likely pathogenic · 8 Conflicting · 16 Benign · 2 Benign/Likely benign · 119 Likely benign · 355 Uncertain significance

Full POLR2A gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 301

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 2

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

Predictors agree, ClinVar conflicts 5

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 197

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 197

Predictors split 96

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

All POLR2A variants

Pathogenic 6

  • p.Ile457Thr Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Leu509fs Single submitter
  • p.Tyr763Ter Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Gln700Ter No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Leu1124Pro No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Thr736Met No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities

Pathogenic/Likely pathogenic 5

  • p.Arg1123Gln Multiple submitters Inborn genetic diseases
  • p.Arg1810Ter Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Glu1289Lys Multiple submitters Inborn genetic diseases
  • p.Ser1094Phe Multiple submitters neurodevelopmental disorder
  • p.Val488Met Multiple submitters Severe global developmental delay

Likely pathogenic 29

  • p.Arg460Gln Multiple submitters POLR2A-related disorder
  • p.Ala748fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Arg1123Gly Single submitter Inborn genetic diseases
  • p.Arg1123Leu Single submitter
  • p.Arg734Gln Single submitter ⚠
  • p.Arg734Trp Single submitter
  • p.Asn1251Ser Single submitter Inborn genetic diseases ⚠
  • p.Asn410Tyr Single submitter
  • p.Asp454fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Gln735Ter Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Gly1238Ser Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Ile714Thr Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Leu236Val Single submitter
  • p.Leu484Phe Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Leu725fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Lys1234Glu Single submitter
  • p.Met248Leu Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Met450fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Met467fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Pro371Leu Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Ser1094Tyr Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Ser648Ter Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Ser8fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Thr1912Ala Single submitter ⚠
  • p.Tyr1720fs Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.His439_Leu440del No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Leu1127Phe No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Lys1125del No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Thr1136Ile No assertion criteria neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities

Conflicting classifications of pathogenicity 8

  • p.Ala270Thr Single submitter Inborn genetic diseases ⚠
  • p.Arg140Trp Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Arg921His Single submitter Inborn genetic diseases ⚠
  • p.Asn722Ser Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Asn723del Single submitter Inborn genetic diseases
  • p.Asp1250Gly Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Gln210Ter Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠
  • p.Val260Met Single submitter neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities ⚠

Benign 16

  • c.1461-44G>A Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • c.1672-16A>C Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • c.1881+42G>A Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • c.2349+26C>T Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • c.538-42C>T Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Asn320= Multiple submitters
  • p.Asn764= Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • p.Phe1202= Multiple submitters
  • p.Pro1837_Lys1838= Multiple submitters
  • p.Ser1147= Multiple submitters
  • p.Ser487= Multiple submitters neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities
  • c.3813+8G>A No assertion criteria POLR2A-related disorder
  • c.94-16CTTT[2] No assertion criteria POLR2A-related disorder
  • p.Arg51= No assertion criteria POLR2A-related disorder
  • p.Gly157= No assertion criteria POLR2A-related disorder
  • p.Thr1184= No assertion criteria POLR2A-related disorder

Benign/Likely benign 2

Likely benign 119

Uncertain significance 355

Showing the top 300 by review status; the full set is in the sitemap.