Sugi Variant

Sugi Variant/PHOX2B

PHOX2B — 1045 ClinVar variants

All ClinVar germline PHOX2B variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 522 flagged for review →

37 Pathogenic · 4 Pathogenic/Likely pathogenic · 19 Likely pathogenic · 35 Conflicting · 17 Benign · 5 Benign/Likely benign · 289 Likely benign · 639 Uncertain significance

Full PHOX2B gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 522

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 17

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 324

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 324

Predictors split 180

The independent predictors disagree with each other — read with care. · showing the 150 best-reviewed of 180

All PHOX2B variants

Pathogenic 37

Pathogenic/Likely pathogenic 4

  • c.242-1G>A Multiple submitters hereditary neoplastic syndrome
  • p.Arg141Gln Multiple submitters hereditary neoplastic syndrome
  • p.Tyr14Ter Multiple submitters hereditary neoplastic syndrome
  • p.Tyr83Ter Multiple submitters hereditary neoplastic syndrome

Likely pathogenic 19

  • c.241+1G>A Multiple submitters Haddad syndrome
  • c.429+1G>A Single submitter hereditary neoplastic syndrome
  • c.429+1G>T Single submitter hereditary neoplastic syndrome
  • p.Ala266_Gly267insAlaAlaAlaAlaAlaAlaAlaGlyGlyLeuAlaAlaAla Single submitter central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
  • p.Arg99Trp Single submitter hereditary neoplastic syndrome
  • p.Asn203fs Single submitter central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
  • p.Gln109fs Single submitter Congenital central hypoventilation syndrome, with or without Hirschsprung disease
  • p.Glu129Gly Single submitter PHOX2B-related disorder
  • p.Gly170fs Single submitter Hirschsprung disease-ganglioneuroblastoma syndrome
  • p.Gly197fs Single submitter PHOX2B-related disorder
  • p.Gly231fs Single submitter central hypoventilation syndrome, congenital
  • p.Gly233fs Single submitter PHOX2B-related disorder
  • p.Leu70fs Single submitter hereditary neoplastic syndrome
  • p.Lys238Ter Single submitter neuroblastoma, susceptibility to, 2
  • p.Phe117fs Single submitter central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
  • p.Pro192fs Single submitter
  • p.Pro236fs Single submitter PHOX2B-related disorder
  • p.Arg149Gly No assertion criteria Hirschsprung disease
  • p.Gly270fs No assertion criteria PHOX2B-related disorder

Conflicting classifications of pathogenicity 35

Benign 17

  • c.242-115G>A Multiple submitters
  • c.429+101A>G Multiple submitters
  • c.430-172A>C Multiple submitters
  • c.*1347A>G Multiple submitters central hypoventilation syndrome, congenital
  • c.*1364G>A Multiple submitters neuroblastoma, susceptibility to, 2
  • c.*1387C>T Multiple submitters central hypoventilation syndrome, congenital
  • c.*161G>A Multiple submitters central hypoventilation syndrome, congenital
  • c.*1662A>T Multiple submitters neuroblastoma, susceptibility to, 2
  • c.*1126C>G Single submitter neuroblastoma, susceptibility to, 2
  • c.*1156C>A Single submitter central hypoventilation syndrome, congenital
  • c.*12GCG[4] Single submitter
  • c.*1381C>T Single submitter neuroblastoma, susceptibility to, 2
  • c.*194C>T Single submitter central hypoventilation syndrome, congenital
  • c.*278T>A Single submitter central hypoventilation syndrome, congenital
  • c.*550G>A Single submitter neuroblastoma, susceptibility to, 2
  • c.*600T>G Single submitter central hypoventilation syndrome, congenital
  • c.*838A>G Single submitter neuroblastoma, susceptibility to, 2

Benign/Likely benign 5

  • c.*80G>A Multiple submitters central hypoventilation syndrome, congenital
  • p.Ala162= Multiple submitters hereditary neoplastic syndrome
  • p.Ser184= Multiple submitters central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease
  • p.Ser24Pro Multiple submitters hereditary neoplastic syndrome ⚠
  • p.Tyr78= Multiple submitters hereditary neoplastic syndrome

Likely benign 289

  • c.242-4C>G Multiple submitters hereditary neoplastic syndrome
  • c.430-6G>C Multiple submitters Haddad syndrome
  • p.Ala108= Multiple submitters hereditary neoplastic syndrome
  • p.Ala108Thr Multiple submitters hereditary neoplastic syndrome
  • p.Ala118= Multiple submitters hereditary neoplastic syndrome
  • p.Ala140= Multiple submitters hereditary neoplastic syndrome
  • p.Ala160= Multiple submitters hereditary neoplastic syndrome
  • p.Ala161= Multiple submitters hereditary neoplastic syndrome
  • p.Ala163= Multiple submitters hereditary neoplastic syndrome
  • p.Ala164= Multiple submitters hereditary neoplastic syndrome
  • p.Ala165= Multiple submitters hereditary neoplastic syndrome
  • p.Ala166= Multiple submitters hereditary neoplastic syndrome
  • p.Ala19= Multiple submitters hereditary neoplastic syndrome
  • p.Ala226= Multiple submitters hereditary neoplastic syndrome
  • p.Ala227= Multiple submitters hereditary neoplastic syndrome
  • p.Ala243= Multiple submitters Haddad syndrome
  • p.Ala244= Multiple submitters hereditary neoplastic syndrome
  • p.Ala245= Multiple submitters hereditary neoplastic syndrome
  • p.Ala246= Multiple submitters Haddad syndrome
  • p.Ala247= Multiple submitters hereditary neoplastic syndrome
  • p.Ala248= Multiple submitters hereditary neoplastic syndrome
  • p.Ala250= Multiple submitters hereditary neoplastic syndrome
  • p.Ala251= Multiple submitters hereditary neoplastic syndrome
  • p.Ala252= Multiple submitters hereditary neoplastic syndrome
  • p.Ala253= Multiple submitters Haddad syndrome
  • p.Ala254= Multiple submitters Haddad syndrome
  • p.Ala259= Multiple submitters hereditary neoplastic syndrome
  • p.Ala260del Multiple submitters hereditary neoplastic syndrome
  • p.Ala265= Multiple submitters hereditary neoplastic syndrome
  • p.Ala266= Multiple submitters hereditary neoplastic syndrome
  • p.Ala306= Multiple submitters hereditary neoplastic syndrome
  • p.Ala39= Multiple submitters hereditary neoplastic syndrome
  • p.Ala53= Multiple submitters Haddad syndrome
  • p.Arg100= Multiple submitters Haddad syndrome
  • p.Arg102= Multiple submitters hereditary neoplastic syndrome
  • p.Arg115= Multiple submitters hereditary neoplastic syndrome
  • p.Arg141= Multiple submitters Haddad syndrome
  • p.Arg150= Multiple submitters hereditary neoplastic syndrome
  • p.Arg158= Multiple submitters hereditary neoplastic syndrome
  • p.Arg71= Multiple submitters hereditary neoplastic syndrome
  • p.Arg96= Multiple submitters hereditary neoplastic syndrome
  • p.Asn302= Multiple submitters hereditary neoplastic syndrome
  • p.Asn45= Multiple submitters hereditary neoplastic syndrome
  • p.Asp136= Multiple submitters hereditary neoplastic syndrome
  • p.Asp177= Multiple submitters hereditary neoplastic syndrome
  • p.Asp181= Multiple submitters Haddad syndrome
  • p.Cys17= Multiple submitters hereditary neoplastic syndrome
  • p.Cys208= Multiple submitters hereditary neoplastic syndrome
  • p.Cys57= Multiple submitters hereditary neoplastic syndrome
  • p.Gln38= Multiple submitters Haddad syndrome
  • p.Gln74= Multiple submitters hereditary neoplastic syndrome
  • p.Glu139= Multiple submitters hereditary neoplastic syndrome
  • p.Glu15= Multiple submitters hereditary neoplastic syndrome
  • p.Glu183= Multiple submitters hereditary neoplastic syndrome
  • p.Glu186= Multiple submitters hereditary neoplastic syndrome
  • p.Gly170= Multiple submitters hereditary neoplastic syndrome
  • p.Gly213= Multiple submitters hereditary neoplastic syndrome
  • p.Gly217= Multiple submitters Haddad syndrome
  • p.Gly225= Multiple submitters hereditary neoplastic syndrome
  • p.Gly230= Multiple submitters hereditary neoplastic syndrome
  • p.Gly231= Multiple submitters hereditary neoplastic syndrome
  • p.Gly240= Multiple submitters hereditary neoplastic syndrome
  • p.Gly267= Multiple submitters hereditary neoplastic syndrome
  • p.Gly270= Multiple submitters Haddad syndrome
  • p.Gly276= Multiple submitters hereditary neoplastic syndrome
  • p.Gly278= Multiple submitters hereditary neoplastic syndrome
  • p.Gly289= Multiple submitters hereditary neoplastic syndrome
  • p.Gly63= Multiple submitters hereditary neoplastic syndrome
  • p.Gly68= Multiple submitters hereditary neoplastic syndrome
  • p.Gly90= Multiple submitters hereditary neoplastic syndrome
  • p.His73= Multiple submitters Haddad syndrome
  • p.His89= Multiple submitters hereditary neoplastic syndrome
  • p.Ile135= Multiple submitters hereditary neoplastic syndrome
  • p.Ile280= Multiple submitters Haddad syndrome
  • p.Leu133= Multiple submitters Haddad syndrome
  • p.Leu137= Multiple submitters hereditary neoplastic syndrome
  • p.Leu287= Multiple submitters hereditary neoplastic syndrome
  • p.Leu67= Multiple submitters hereditary neoplastic syndrome
  • p.Leu70= Multiple submitters hereditary neoplastic syndrome
  • p.Lys155= Multiple submitters hereditary neoplastic syndrome
  • p.Lys168= Multiple submitters hereditary neoplastic syndrome
  • p.Lys174= Multiple submitters Haddad syndrome
  • p.Lys3= Multiple submitters hereditary neoplastic syndrome
  • p.Phe117= Multiple submitters hereditary neoplastic syndrome
  • p.Phe153= Multiple submitters hereditary neoplastic syndrome
  • p.Phe314= Multiple submitters Haddad syndrome
  • p.Phe33= Multiple submitters hereditary neoplastic syndrome
  • p.Phe51= Multiple submitters Haddad syndrome
  • p.Pro123= Multiple submitters Haddad syndrome
  • p.Pro192= Multiple submitters hereditary neoplastic syndrome
  • p.Pro200= Multiple submitters Haddad syndrome
  • p.Pro204= Multiple submitters hereditary neoplastic syndrome
  • p.Pro220= Multiple submitters hereditary neoplastic syndrome
  • p.Pro224= Multiple submitters hereditary neoplastic syndrome
  • p.Pro229= Multiple submitters hereditary neoplastic syndrome
  • p.Pro236= Multiple submitters hereditary neoplastic syndrome
  • p.Pro269= Multiple submitters hereditary neoplastic syndrome
  • p.Pro275= Multiple submitters hereditary neoplastic syndrome
  • p.Pro277= Multiple submitters hereditary neoplastic syndrome
  • p.Pro290= Multiple submitters hereditary neoplastic syndrome
  • p.Pro46= Multiple submitters Haddad syndrome
  • p.Pro46= Multiple submitters hereditary neoplastic syndrome
  • p.Pro58= Multiple submitters Haddad syndrome
  • p.Pro62= Multiple submitters Haddad syndrome
  • p.Pro62= Multiple submitters Haddad syndrome
  • p.Pro77= Multiple submitters hereditary neoplastic syndrome
  • p.Pro77= Multiple submitters hereditary neoplastic syndrome
  • p.Pro82= Multiple submitters Haddad syndrome
  • p.Ser12= Multiple submitters hereditary neoplastic syndrome
  • p.Ser16= Multiple submitters hereditary neoplastic syndrome
  • p.Ser171= Multiple submitters hereditary neoplastic syndrome
  • p.Ser219= Multiple submitters hereditary neoplastic syndrome
  • p.Ser24= Multiple submitters hereditary neoplastic syndrome
  • p.Ser28= Multiple submitters Haddad syndrome
  • p.Ser297= Multiple submitters hereditary neoplastic syndrome
  • p.Ser37= Multiple submitters Haddad syndrome
  • p.Ser40= Multiple submitters hereditary neoplastic syndrome
  • p.Ser55= Multiple submitters Haddad syndrome
  • p.Ser55= Multiple submitters hereditary neoplastic syndrome
  • p.Ser76= Multiple submitters hereditary neoplastic syndrome
  • p.Thr120= Multiple submitters hereditary neoplastic syndrome
  • p.Thr127= Multiple submitters Haddad syndrome
  • p.Thr190= Multiple submitters hereditary neoplastic syndrome
  • p.Thr23= Multiple submitters hereditary neoplastic syndrome
  • p.Thr281= Multiple submitters hereditary neoplastic syndrome
  • p.Thr54= Multiple submitters hereditary neoplastic syndrome
  • p.Thr61= Multiple submitters hereditary neoplastic syndrome
  • p.Thr61= Multiple submitters Haddad syndrome
  • p.Thr69= Multiple submitters hereditary neoplastic syndrome
  • p.Tyr126= Multiple submitters Haddad syndrome
  • p.Tyr44= Multiple submitters hereditary neoplastic syndrome
  • p.Tyr83= Multiple submitters hereditary neoplastic syndrome
  • p.Val294= Multiple submitters hereditary neoplastic syndrome
  • p.Val309= Multiple submitters hereditary neoplastic syndrome
  • p.Val81= Multiple submitters hereditary neoplastic syndrome
  • c.241+10T>A Single submitter Haddad syndrome
  • c.241+11_241+12del Single submitter Haddad syndrome
  • c.241+12C>T Single submitter Haddad syndrome
  • c.241+13A>C Single submitter Haddad syndrome
  • c.241+15C>T Single submitter Haddad syndrome
  • c.241+19del Single submitter Haddad syndrome
  • c.241+8C>T Single submitter Haddad syndrome
  • c.241+9C>T Single submitter Haddad syndrome
  • c.242-114G>T Single submitter
  • c.242-12G>A Single submitter Haddad syndrome
  • c.242-13T>C Single submitter Haddad syndrome
  • c.242-14C>T Single submitter Haddad syndrome
  • c.242-16del Single submitter Haddad syndrome
  • c.242-17C>T Single submitter Haddad syndrome
  • c.242-18T>C Single submitter Haddad syndrome
  • c.242-20T>A Single submitter Haddad syndrome
  • c.242-20T>C Single submitter Haddad syndrome
  • c.242-5T>G Single submitter hereditary neoplastic syndrome
  • c.242-7A>G Single submitter Haddad syndrome
  • c.242-8T>C Single submitter Haddad syndrome
  • c.242-9A>G Single submitter Haddad syndrome
  • c.429+10C>T Single submitter Haddad syndrome
  • c.429+12T>A Single submitter Haddad syndrome
  • c.429+13G>A Single submitter Haddad syndrome
  • c.429+13G>C Single submitter Haddad syndrome
  • c.429+14del Single submitter Haddad syndrome
  • c.429+18C>T Single submitter Haddad syndrome
  • c.429+19C>A Single submitter Haddad syndrome
  • c.429+19C>G Single submitter Haddad syndrome
  • c.429+19del Single submitter Haddad syndrome
  • c.429+5GC[2] Single submitter Haddad syndrome
  • c.429+7G>T Single submitter central hypoventilation syndrome, congenital
  • c.429+80G>T Single submitter
  • c.429+8C>A Single submitter Haddad syndrome
  • c.429+8C>G Single submitter Haddad syndrome
  • c.429+8C>T Single submitter Haddad syndrome
  • c.429+9G>A Single submitter Haddad syndrome
  • c.429+9G>C Single submitter Haddad syndrome
  • c.429+9G>T Single submitter Haddad syndrome
  • c.430-11T>C Single submitter Haddad syndrome
  • c.430-12G>A Single submitter Haddad syndrome
  • c.430-13C>T Single submitter Haddad syndrome
  • c.430-15T>G Single submitter Haddad syndrome
  • c.430-18C>T Single submitter Haddad syndrome
  • c.430-19T>C Single submitter Haddad syndrome
  • c.430-20C>G Single submitter Haddad syndrome
  • c.430-20C>T Single submitter Haddad syndrome
  • c.430-7G>C Single submitter Haddad syndrome
  • c.430-8T>C Single submitter Haddad syndrome
  • c.430-8T>G Single submitter Haddad syndrome
  • p.Ala13= Single submitter hereditary neoplastic syndrome
  • p.Ala132= Single submitter hereditary neoplastic syndrome
  • p.Ala151= Single submitter hereditary neoplastic syndrome
  • p.Ala159= Single submitter hereditary neoplastic syndrome
  • p.Ala187= Single submitter hereditary neoplastic syndrome
  • p.Ala210= Single submitter hereditary neoplastic syndrome
  • p.Ala221= Single submitter hereditary neoplastic syndrome
  • p.Ala223= Single submitter
  • p.Ala241= Single submitter hereditary neoplastic syndrome
  • p.Ala242= Single submitter hereditary neoplastic syndrome
  • p.Ala255= Single submitter hereditary neoplastic syndrome
  • p.Ala260= Single submitter hereditary neoplastic syndrome
  • p.Ala264= Single submitter
  • p.Ala27= Single submitter hereditary neoplastic syndrome
  • p.Ala29= Single submitter hereditary neoplastic syndrome
  • p.Ala292= Single submitter hereditary neoplastic syndrome
  • p.Ala307= Single submitter hereditary neoplastic syndrome
  • p.Ala31= Single submitter hereditary neoplastic syndrome
  • p.Ala53= Single submitter hereditary neoplastic syndrome
  • p.Ala79= Single submitter hereditary neoplastic syndrome
  • p.Arg154= Single submitter Haddad syndrome
  • p.Arg180= Single submitter
  • p.Arg99= Single submitter Haddad syndrome
  • p.Asn169= Single submitter hereditary neoplastic syndrome
  • p.Asn201= Single submitter
  • p.Asn211= Single submitter hereditary neoplastic syndrome
  • p.Asn93= Single submitter Haddad syndrome
  • p.Asp124= Single submitter hereditary neoplastic syndrome
  • p.Asp182= Single submitter hereditary neoplastic syndrome
  • p.Asp191= Single submitter
  • p.Asp193= Single submitter hereditary neoplastic syndrome
  • p.Cys65= Single submitter hereditary neoplastic syndrome
  • p.Gln43= Single submitter hereditary neoplastic syndrome
  • p.Glu112= Single submitter hereditary neoplastic syndrome
  • p.Glu129= Single submitter Haddad syndrome
  • p.Glu235= Single submitter Haddad syndrome
  • p.Glu235Gln Single submitter hereditary neoplastic syndrome
  • p.Glu5= Single submitter hereditary neoplastic syndrome
  • p.Gly173= Single submitter hereditary neoplastic syndrome
  • p.Gly199= Single submitter
  • p.Gly209= Single submitter hereditary neoplastic syndrome
  • p.Gly212= Single submitter hereditary neoplastic syndrome
  • p.Gly214= Single submitter hereditary neoplastic syndrome
  • p.Gly215= Single submitter hereditary neoplastic syndrome
  • p.Gly216= Single submitter Haddad syndrome
  • p.Gly228= Single submitter hereditary neoplastic syndrome
  • p.Gly233= Single submitter Haddad syndrome
  • p.Gly234= Single submitter hereditary neoplastic syndrome
  • p.Gly237= Single submitter Haddad syndrome
  • p.Gly239= Single submitter Haddad syndrome
  • p.Gly268= Single submitter hereditary neoplastic syndrome
  • p.Gly288= Single submitter Haddad syndrome
  • p.Gly303= Single submitter hereditary neoplastic syndrome
  • p.Gly52= Single submitter hereditary neoplastic syndrome
  • p.Gly56= Single submitter hereditary neoplastic syndrome
  • p.Gly91= Single submitter hereditary neoplastic syndrome
  • p.Ile101= Single submitter Haddad syndrome
  • p.Ile125= Single submitter hereditary neoplastic syndrome
  • p.Ile283= Single submitter Haddad syndrome
  • p.Leu110= Single submitter Haddad syndrome
  • p.Leu113= Single submitter hereditary neoplastic syndrome
  • p.Leu131= Single submitter hereditary neoplastic syndrome
  • p.Leu26= Single submitter hereditary neoplastic syndrome
  • p.Leu263= Single submitter Haddad syndrome
  • p.Leu295= Single submitter hereditary neoplastic syndrome
  • p.Leu298= Single submitter hereditary neoplastic syndrome
  • p.Leu308= Single submitter hereditary neoplastic syndrome
  • p.Leu85= Single submitter hereditary neoplastic syndrome
  • p.Leu9= Single submitter hereditary neoplastic syndrome
  • p.Lys152= Single submitter hereditary neoplastic syndrome
  • p.Lys188= Single submitter hereditary neoplastic syndrome
  • p.Lys238= Single submitter Haddad syndrome
  • p.Lys84= Single submitter hereditary neoplastic syndrome
  • p.Lys95= Single submitter hereditary neoplastic syndrome
  • p.Pro198= Single submitter
  • p.Pro202= Single submitter hereditary neoplastic syndrome
  • p.Pro206= Single submitter hereditary neoplastic syndrome
  • p.Pro232= Single submitter hereditary neoplastic syndrome
  • p.Pro279= Single submitter Haddad syndrome
  • p.Pro301= Single submitter hereditary neoplastic syndrome
  • p.Ser172= Single submitter Haddad syndrome
  • p.Ser176= Single submitter hereditary neoplastic syndrome
  • p.Ser178= Single submitter
  • p.Ser179= Single submitter Haddad syndrome
  • p.Ser194= Single submitter hereditary neoplastic syndrome
  • p.Ser207= Single submitter hereditary neoplastic syndrome
  • p.Ser286= Single submitter hereditary neoplastic syndrome
  • p.Ser296= Single submitter hereditary neoplastic syndrome
  • p.Ser34= Single submitter Haddad syndrome
  • p.Ser35= Single submitter hereditary neoplastic syndrome
  • p.Ter315= Single submitter hereditary neoplastic syndrome
  • p.Thr103= Single submitter hereditary neoplastic syndrome
  • p.Thr104= Single submitter hereditary neoplastic syndrome
  • p.Thr106= Single submitter hereditary neoplastic syndrome
  • p.Thr138= Single submitter hereditary neoplastic syndrome
  • p.Thr205= Single submitter hereditary neoplastic syndrome
  • p.Thr49= Single submitter Haddad syndrome
  • p.Thr54= Single submitter Haddad syndrome
  • p.Thr87= Single submitter hereditary neoplastic syndrome
  • p.Tyr122= Single submitter hereditary neoplastic syndrome
  • p.Tyr2= Single submitter hereditary neoplastic syndrome
  • p.Tyr8= Single submitter hereditary neoplastic syndrome
  • p.Val116= Single submitter Haddad syndrome
  • p.Val142= Single submitter Haddad syndrome

Uncertain significance 639

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