Sugi Variant

Sugi Variant/OTOF

OTOF — 2241 ClinVar variants

All ClinVar germline OTOF variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 533 flagged for review →

202 Pathogenic · 29 Pathogenic/Likely pathogenic · 142 Likely pathogenic · 224 Conflicting · 103 Benign · 52 Benign/Likely benign · 995 Likely benign · 494 Uncertain significance

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

⚑ Evidence disagreements 533

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 106

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

Predictors lean, ClinVar uncertain 290

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 290

Predictors split 134

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

All OTOF variants

Pathogenic 202

Pathogenic/Likely pathogenic 29

  • c.1045+2T>G Multiple submitters Rare genetic deafness
  • c.3289-1G>C Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • c.3409-2A>C Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • c.3864+1G>A Multiple submitters Rare genetic deafness
  • c.4961-1G>A Multiple submitters Bilateral sensorineural hearing impairment
  • p.Arg1583Cys Multiple submitters OTOF-related disorder
  • p.Arg1792His Multiple submitters Rare genetic deafness
  • p.Arg1856Gln Multiple submitters nonsyndromic genetic hearing loss ⚠
  • p.Arg1939Gln Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Arg26Ter Multiple submitters nonsyndromic genetic hearing loss
  • p.Glu643Ter Multiple submitters Rare genetic deafness
  • p.Gly280fs Multiple submitters Rare genetic deafness
  • p.Ile1108fs Multiple submitters auditory neuropathy
  • p.Ile1573Thr Multiple submitters OTOF-related disorder
  • p.Ile851_Trp852insTer Multiple submitters
  • p.Leu1209fs Multiple submitters Rare genetic deafness
  • p.Leu1934fs Multiple submitters OTOF-related disorder
  • p.Lys1811Ter Multiple submitters Bilateral sensorineural hearing impairment
  • p.Lys391fs Multiple submitters nonsyndromic genetic hearing loss
  • p.Ser11Ter Multiple submitters OTOF-related disorder
  • p.Trp1889Ter Multiple submitters nonsyndromic genetic hearing loss
  • p.Trp1890Arg Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Trp356Ter Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Trp50Ter Multiple submitters nonsyndromic genetic hearing loss
  • p.Val456fs Multiple submitters OTOF-related disorder
  • p.Glu1733Lys No assertion criteria Auditory neuropathy spectrum disorder
  • p.Gly1905Val No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Ile1126fs No assertion criteria hearing loss, autosomal recessive
  • p.Val635Asp No assertion criteria autosomal recessive nonsyndromic hearing loss 9

Likely pathogenic 142

  • c.2215-1G>C Expert panel autosomal recessive nonsyndromic hearing loss 9
  • c.5193-1G>A Expert panel nonsyndromic genetic hearing loss
  • p.Arg1583His Expert panel autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1792Cys Expert panel nonsyndromic genetic hearing loss
  • c.1912+1G>C Multiple submitters tricho-oculo-dermo-vertebral syndrome
  • c.2867-5_2881del Multiple submitters OTOF-related disorder
  • c.3734-2A>G Multiple submitters
  • c.4228-1G>A Multiple submitters Rare genetic deafness
  • c.5713-2A>G Multiple submitters
  • c.80-2A>G Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1735Trp Multiple submitters hearing loss disorder
  • p.Asp1514Gly Multiple submitters hearing loss, autosomal recessive
  • p.Gly1654Ser Multiple submitters hearing loss, autosomal recessive ⚠
  • p.Ile1484fs Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Ile515Thr Multiple submitters Rare genetic deafness
  • c.1206-1G>A Single submitter
  • c.139-2A>G Single submitter
  • c.1579+1G>A Single submitter nonsyndromic genetic hearing loss
  • c.1803+1del Single submitter
  • c.1803+1G>A Single submitter
  • c.2214+5G>C Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.227+1G>A Single submitter
  • c.227+2T>C Single submitter
  • c.2316-1G>A Single submitter
  • c.2406+2dup Single submitter auditory neuropathy
  • c.2406+2T>C Single submitter
  • c.2407-2A>C Single submitter
  • c.2677-1G>C Single submitter
  • c.2677-2A>G Single submitter hearing loss disorder
  • c.2839_2867-12del Single submitter
  • c.2866+1G>C Single submitter nonsyndromic genetic hearing loss
  • c.2991+1G>A Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.3126+2T>C Single submitter
  • c.327+2T>G Single submitter
  • c.328-1G>C Single submitter
  • c.328-1G>T Single submitter
  • c.3284_3288+10del Single submitter
  • c.3408+1G>A Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.3409-2A>G Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.3409-2A>T Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.3570+2T>C Single submitter ear malformation
  • c.3733+1G>A Single submitter
  • c.3734-2A>C Single submitter
  • c.3864+2T>C Single submitter
  • c.3895-1G>A Single submitter
  • c.3925_4023+169delinsG Single submitter
  • c.4091-1G>A Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.4091-2A>C Single submitter
  • c.4362+1G>T Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.510-1G>A Single submitter
  • c.5291+1G>T Single submitter auditory neuropathy
  • c.5533+1G>A Single submitter
  • c.5534-2A>G Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.5713-1G>A Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.5812_5813+2del Single submitter
  • c.5813+1G>A Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.765+2T>C Single submitter
  • c.79+1G>A Single submitter OTOF-related disorder
  • c.829_897+276delinsCTGTGAAAGAAC Single submitter
  • c.897+1G>T Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.897+5G>C Single submitter tricho-oculo-dermo-vertebral syndrome
  • c.898-2A>G Single submitter
  • c.960+1G>C Single submitter
  • c.*18-1G>A Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Ala1927Asp Single submitter auditory neuropathy
  • p.Ala969fs Single submitter Bilateral sensorineural hearing impairment
  • p.Arg1080Pro Single submitter Bilateral sensorineural hearing impairment
  • p.Arg1448fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1607Trp Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1635Ter Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1928Cys Single submitter auditory neuropathy
  • p.Arg963Gly Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Asp1777Gly Single submitter auditory neuropathy
  • p.Asp1798fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Asp791fs Single submitter Rare genetic deafness
  • p.Cys927Ter Single submitter auditory neuropathy
  • p.Gln1152Ter Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Gln470Ter Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Gln592Ter Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Gln651Ter Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Gln907Ter Single submitter hearing loss disorder
  • p.Glu1062fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Glu1548fs Single submitter
  • p.Glu1917fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Glu1918fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Gly1905Asp Single submitter tricho-oculo-dermo-vertebral syndrome
  • p.Gly614Glu Single submitter Bilateral sensorineural hearing impairment
  • p.Gly943fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.His513fs Single submitter auditory neuropathy
  • p.Ile1187del Single submitter
  • p.Ile1200del Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Ile1738del Single submitter auditory neuropathy
  • p.Leu1088fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Leu1616Pro Single submitter auditory neuropathy
  • p.Leu1794fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Leu870_Leu871dup Single submitter auditory neuropathy
  • p.Lys464Ter Single submitter
  • p.Lys466fs Single submitter
  • p.Lys834Ter Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Lys896fs Single submitter auditory neuropathy
  • p.Phe613fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Phe872fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Pro1128fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Ser1240fs Single submitter autosomal recessive nonsyndromic hearing loss 3
  • p.Thr395fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Trp1889Ser Single submitter auditory neuropathy
  • p.Trp416Ter Single submitter autosomal recessive nonsyndromic hearing loss 3
  • p.Tyr1497fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • p.Tyr1598fs Single submitter auditory neuropathy
  • p.Tyr455Phe Single submitter OTOF-related disorder ⚠
  • p.Tyr967Ter Single submitter auditory neuropathy
  • p.Val52fs Single submitter nonsyndromic genetic hearing loss
  • p.Val886fs Single submitter autosomal recessive nonsyndromic hearing loss 9
  • c.1046-1G>C No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.1373_1392+1delinsCAGGTACAGCAAAGAAGT No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.1803+2T>C No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.1804-2A>G No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.1912+5G>C No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.1913-50G>A No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.2214+5G>A No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.2524-1G>C No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.2677-20_3894+46del No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.898-1G>A No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • c.961-1G>A No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Ala1230fs No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Ala224fs No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Arg568Trp No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Gln498Pro No assertion criteria Auditory neuropathy spectrum disorder
  • p.Gly1787Asp No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Gly371Asp No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Leu1228Pro No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Leu1934Arg No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Leu1976fs No assertion criteria Rare genetic deafness
  • p.Lys1226Glu No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Lys1859fs No assertion criteria Rare genetic deafness
  • p.Ser1225Cys No assertion criteria autosomal recessive nonsyndromic hearing loss 9 ⚠
  • p.Ser1389fs No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Thr512Ile No assertion criteria Auditory neuropathy spectrum disorder
  • p.Val1296fs No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Val1498Glu No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Val1744Glu No assertion criteria autosomal recessive nonsyndromic hearing loss 9
  • p.Val1778Ala No assertion criteria autosomal recessive nonsyndromic hearing loss 9

Conflicting classifications of pathogenicity 224

Benign 103

Benign/Likely benign 52

  • c.1393-15T>G Multiple submitters
  • c.1579+19G>A Multiple submitters
  • c.1580-7G>T Multiple submitters
  • c.1912+17C>T Multiple submitters
  • c.2215-155A>G Multiple submitters
  • c.2215-19C>G Multiple submitters
  • c.2215-77T>G Multiple submitters
  • c.2215-83C>T Multiple submitters
  • c.228-16C>T Multiple submitters
  • c.2406+19G>A Multiple submitters
  • c.2407-17C>T Multiple submitters
  • c.3734-13T>C Multiple submitters
  • c.4628+18C>T Multiple submitters
  • c.4629-9C>T Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • c.509+10A>G Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • c.510-7del Multiple submitters
  • c.-120G>T Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • c.-67G>A Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • c.*372C>T Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Ala1997= Multiple submitters
  • p.Ala53Val Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1026Trp Multiple submitters ⚠
  • p.Arg14= Multiple submitters
  • p.Arg1589= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Arg1885= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Arg49Trp Multiple submitters autosomal recessive nonsyndromic hearing loss 9 ⚠
  • p.Arg773Cys Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Arg822Trp Multiple submitters autosomal recessive nonsyndromic hearing loss 9 ⚠
  • p.Arg82Cys Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Asn1203Ser Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Asn642= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Asp1660= Multiple submitters
  • p.Asp674= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Cys1251Gly Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Glu675= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Glu801Leu Multiple submitters
  • p.Glu801Ter Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Glu801Val Multiple submitters autosomal recessive nonsyndromic hearing loss 9 ⚠
  • p.Gly123Ser Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Gly943= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Leu13= Multiple submitters
  • p.Leu871= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Lys315= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Pro1128= Multiple submitters
  • p.Pro1646Ser Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Pro309Leu Multiple submitters
  • p.Ser502= Multiple submitters
  • p.Ser901= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Thr1942= Multiple submitters
  • p.Thr395= Multiple submitters autosomal recessive nonsyndromic hearing loss 9
  • p.Tyr1732= Multiple submitters
  • p.Val1559= Multiple submitters autosomal recessive nonsyndromic hearing loss 9

Likely benign 995

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

Uncertain significance 494

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