SPNS2 — 172 ClinVar variants
All ClinVar germline SPNS2 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 97 flagged for review →
3 Likely pathogenic · 34 Benign · 3 Benign/Likely benign · 27 Likely benign · 105 Uncertain significance
Full SPNS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 97
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 lean, ClinVar uncertain 83
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
- SPNS2 p.Ala545Thr Uncertain significance Multiple submitters
- SPNS2 p.Ala289Thr Uncertain significance Single submitter
- SPNS2 p.Ala30Thr Uncertain significance Single submitter
- SPNS2 p.Ala328Thr Uncertain significance Single submitter
- SPNS2 p.Ala331Ser Uncertain significance Single submitter
- SPNS2 p.Ala441Val Uncertain significance Single submitter
- SPNS2 p.Ala459Thr Uncertain significance Single submitter
- SPNS2 p.Ala473Thr Uncertain significance Single submitter
- SPNS2 p.Ala521Thr Uncertain significance Single submitter
- SPNS2 p.Ala545Ser Uncertain significance Single submitter
- SPNS2 p.Ala81Val Uncertain significance Single submitter
- SPNS2 p.Arg164Cys Uncertain significance Single submitter
- SPNS2 p.Arg26Trp Uncertain significance Single submitter
- SPNS2 p.Arg28Pro Uncertain significance Single submitter
- SPNS2 p.Arg299Gln Uncertain significance Single submitter
- SPNS2 p.Arg386His Uncertain significance Single submitter
- SPNS2 p.Arg389Cys Uncertain significance Single submitter
- SPNS2 p.Arg394Gln Uncertain significance Single submitter
- SPNS2 p.Arg455Trp Uncertain significance Single submitter
- SPNS2 p.Arg456Cys Uncertain significance Single submitter
- SPNS2 p.Arg456His Uncertain significance Single submitter
- SPNS2 p.Arg456Leu Uncertain significance Single submitter
- SPNS2 p.Arg487His Uncertain significance Single submitter
- SPNS2 p.Arg65Ser Uncertain significance Single submitter
- SPNS2 p.Arg99His Uncertain significance Single submitter
- SPNS2 p.Asp396Asn Uncertain significance Single submitter
- SPNS2 p.Asp529Asn Uncertain significance Single submitter
- SPNS2 p.Asp55Asn Uncertain significance Single submitter
- SPNS2 p.Cys39Ser Uncertain significance Single submitter
- SPNS2 p.Cys6Arg Uncertain significance Single submitter
- SPNS2 p.Gln291Glu Uncertain significance Single submitter
- SPNS2 p.Gln91Arg Uncertain significance Single submitter
- SPNS2 p.Glu17Asp Uncertain significance Single submitter
- SPNS2 p.Glu18Ala Uncertain significance Single submitter
- SPNS2 p.Glu351Gly Uncertain significance Single submitter
- SPNS2 p.Gly100Glu Uncertain significance Single submitter
- SPNS2 p.Gly139Asp Uncertain significance Single submitter
- SPNS2 p.Gly174Ser Uncertain significance Single submitter
- SPNS2 p.Gly293Arg Uncertain significance Single submitter
- SPNS2 p.Gly41Trp Uncertain significance Single submitter
- SPNS2 p.Gly432Arg Uncertain significance Single submitter
- SPNS2 p.Gly86Arg Uncertain significance Single submitter
- SPNS2 p.Ile213Val Uncertain significance Single submitter
- SPNS2 p.Leu303Val Uncertain significance Single submitter
- SPNS2 p.Leu320Val Uncertain significance Single submitter
- SPNS2 p.Leu364Phe Uncertain significance Single submitter
- SPNS2 p.Leu478Phe Uncertain significance Single submitter
- SPNS2 p.Leu495Phe Uncertain significance Single submitter
- SPNS2 p.Leu507Phe Uncertain significance Single submitter
- SPNS2 p.Lys136Thr Uncertain significance Single submitter
- SPNS2 p.Lys361Glu Uncertain significance Single submitter
- SPNS2 p.Lys491Arg Uncertain significance Single submitter
- SPNS2 p.Met152Thr Uncertain significance Single submitter
- SPNS2 p.Phe177Leu Uncertain significance Single submitter
- SPNS2 p.Pro494Gln Uncertain significance Single submitter
- SPNS2 p.Pro71Ser Uncertain significance Single submitter
- SPNS2 p.Pro71Thr Uncertain significance Single submitter
- SPNS2 p.Pro72Arg Uncertain significance Single submitter
- SPNS2 p.Ser172Gly Uncertain significance Single submitter
- SPNS2 p.Ser51Leu Uncertain significance Single submitter
- SPNS2 p.Ser96Asn Uncertain significance Single submitter
- SPNS2 p.Ser96Thr Uncertain significance Single submitter
- SPNS2 p.Thr228Met Uncertain significance Single submitter
- SPNS2 p.Thr284Asn Uncertain significance Single submitter
- SPNS2 p.Thr284Ile Uncertain significance Single submitter
- SPNS2 p.Thr434Arg Uncertain significance Single submitter
- SPNS2 p.Thr434Met Uncertain significance Single submitter
- SPNS2 p.Thr69Pro Uncertain significance Single submitter
- SPNS2 p.Thr74Pro Uncertain significance Single submitter
- SPNS2 p.Thr77Pro Uncertain significance Single submitter
- SPNS2 p.Trp194Arg Uncertain significance Single submitter
- SPNS2 p.Val181Ile Uncertain significance Single submitter
- SPNS2 p.Val233Ile Uncertain significance Single submitter
- SPNS2 p.Val252Leu Uncertain significance Single submitter
- SPNS2 p.Val268Leu Uncertain significance Single submitter
- SPNS2 p.Val316Ile Uncertain significance Single submitter
- SPNS2 p.Val399Met Uncertain significance Single submitter
- SPNS2 p.Val416Met Uncertain significance Single submitter
- SPNS2 p.Val423Ile Uncertain significance Single submitter
- SPNS2 p.Val423Leu Uncertain significance Single submitter
- SPNS2 p.Val527Ile Uncertain significance Single submitter
- SPNS2 p.Val64Leu Uncertain significance Single submitter
-
SPNS2 p.Asp163Asn
Uncertain significance
No assertion criteria
sensorineural hearing loss disorder
Predictors split 14
The independent predictors disagree with each other — read with care.
-
SPNS2 p.Ala401Thr
Uncertain significance
Multiple submitters
microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
- SPNS2 p.Arg164His Uncertain significance Single submitter
- SPNS2 p.Arg299Trp Uncertain significance Single submitter
- SPNS2 p.Arg455Gln Uncertain significance Single submitter
- SPNS2 p.Arg487Cys Uncertain significance Single submitter
- SPNS2 p.Cys353Ser Uncertain significance Single submitter
- SPNS2 p.Gly257Arg Uncertain significance Single submitter
- SPNS2 p.Met506Ile Uncertain significance Single submitter
- SPNS2 p.Phe317Leu Uncertain significance Single submitter
- SPNS2 p.Phe518Ser Uncertain significance Single submitter
-
SPNS2 p.Pro215Ala
Uncertain significance
Single submitter
hearing loss disorder
-
SPNS2 p.Pro509Ser
Uncertain significance
Single submitter
hearing loss, autosomal recessive 115
- SPNS2 p.Thr300Ala Uncertain significance Single submitter
- SPNS2 p.Val399Leu Uncertain significance Single submitter
All SPNS2 variants
Likely pathogenic 3
- p.Lys93fs Single submitter hearing loss, autosomal recessive 115
- p.Pro356Cysfs Single submitter Inborn genetic diseases
- p.Trp302Ter No assertion criteria sensorineural hearing loss disorder
Benign 34
- c.1279-152G>A Multiple submitters
- c.1344+66C>T Multiple submitters
- c.1345-58A>G Multiple submitters
- c.1345-89G>A Multiple submitters
- c.1443+27C>A Multiple submitters
- c.1443+28A>G Multiple submitters hearing loss, autosomal recessive 115
- c.1443+32C>G Multiple submitters hearing loss, autosomal recessive 115
- c.1443+43A>G Multiple submitters hearing loss, autosomal recessive 115
- c.1444-26T>C Multiple submitters hearing loss, autosomal recessive 115
- c.1444-43G>T Multiple submitters
- c.1607+107A>C Multiple submitters
- c.1607+74C>G Multiple submitters
- c.1607+88G>C Multiple submitters
- c.370+91T>C Multiple submitters
- c.436+31G>A Multiple submitters hearing loss, autosomal recessive 115
- c.436+67T>C Multiple submitters
- c.792+36C>T Multiple submitters
- c.792+57G>C Multiple submitters
- c.935+26T>C Multiple submitters hearing loss, autosomal recessive 115
- c.-153G>C Multiple submitters
- c.1278+142C>T Single submitter
- c.1278+170G>A Single submitter
- c.1607+10_1607+11insA Single submitter
- c.1607+12_1607+13dup Single submitter
- c.1607+13_1607+14insGA Single submitter
- c.1608-14C>T Single submitter
- c.573+52G>T Single submitter
- c.574-104C>G Single submitter
- c.793-170G>A Single submitter
- p.Ala531Thr Single submitter
- c.726-3C>T No assertion criteria SPNS2-related disorder
- p.Ala408Ser No assertion criteria SPNS2-related disorder
- p.Thr322= No assertion criteria SPNS2-related disorder
- p.Val203= No assertion criteria SPNS2-related disorder
Benign/Likely benign 3
- c.1607+13dup Multiple submitters
- p.Ala523= Multiple submitters
- p.Leu340= Multiple submitters hearing loss, autosomal recessive 115
Likely benign 27
- c.1278+12G>A Single submitter
- c.1607+11_1607+13dup Single submitter
- p.Ala154= Single submitter
- p.Ala180= Single submitter
- p.Ala417Thr Single submitter
- p.Ala504= Single submitter
- p.Ala541Val Single submitter
- p.Arg342= Single submitter
- p.Ile310= Single submitter
- p.Phe327= Single submitter
- p.Phe415= Single submitter
- p.Pro71= Single submitter
- p.Pro72= Single submitter
- p.Tyr449= Single submitter
- p.Val268Ile Single submitter
- c.1607+9G>C No assertion criteria SPNS2-related disorder
- c.792+5G>A No assertion criteria SPNS2-related disorder
- c.935+3G>T No assertion criteria SPNS2-related disorder
- p.Ala289= No assertion criteria SPNS2-related disorder
- p.Ala321Gly No assertion criteria SPNS2-related disorder
- p.Arg456= No assertion criteria SPNS2-related disorder
- p.Arg530= No assertion criteria SPNS2-related disorder
- p.Gly12= No assertion criteria SPNS2-related disorder
- p.Gly139= No assertion criteria SPNS2-related disorder
- p.Thr454= No assertion criteria SPNS2-related disorder
- p.Val125Ile No assertion criteria SPNS2-related disorder
- p.Val431Ile No assertion criteria SPNS2-related disorder
Uncertain significance 105
- p.Ala401Thr Multiple submitters microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome ⚠
- p.Ala545Thr Multiple submitters ⚠
- c.1088+5G>A Single submitter hearing loss, autosomal recessive 115
- p.Ala289Thr Single submitter ⚠
- p.Ala30Thr Single submitter ⚠
- p.Ala328Thr Single submitter ⚠
- p.Ala331Ser Single submitter ⚠
- p.Ala441Val Single submitter ⚠
- p.Ala459Thr Single submitter ⚠
- p.Ala473Thr Single submitter ⚠
- p.Ala521Thr Single submitter ⚠
- p.Ala545Ser Single submitter ⚠
- p.Ala81Val Single submitter ⚠
- p.Arg164Cys Single submitter ⚠
- p.Arg164His Single submitter ⚠
- p.Arg26Trp Single submitter ⚠
- p.Arg28Pro Single submitter ⚠
- p.Arg299Gln Single submitter ⚠
- p.Arg299Trp Single submitter ⚠
- p.Arg386His Single submitter ⚠
- p.Arg389Cys Single submitter ⚠
- p.Arg394Gln Single submitter ⚠
- p.Arg394Trp Single submitter
- p.Arg455Gln Single submitter ⚠
- p.Arg455Trp Single submitter ⚠
- p.Arg456Cys Single submitter ⚠
- p.Arg456His Single submitter ⚠
- p.Arg456Leu Single submitter ⚠
- p.Arg487Cys Single submitter ⚠
- p.Arg487His Single submitter ⚠
- p.Arg65Ser Single submitter ⚠
- p.Arg99His Single submitter ⚠
- p.Asp396Asn Single submitter ⚠
- p.Asp529Asn Single submitter ⚠
- p.Asp55Asn Single submitter ⚠
- p.Cys353Ser Single submitter ⚠
- p.Cys39Ser Single submitter ⚠
- p.Cys412Gly Single submitter
- p.Cys6Arg Single submitter ⚠
- p.Gln291Glu Single submitter ⚠
- p.Gln91Arg Single submitter ⚠
- p.Glu17Asp Single submitter ⚠
- p.Glu18Ala Single submitter ⚠
- p.Glu351Gly Single submitter ⚠
- p.Gly100Glu Single submitter ⚠
- p.Gly139Asp Single submitter ⚠
- p.Gly174Ser Single submitter ⚠
- p.Gly257Arg Single submitter ⚠
- p.Gly293Arg Single submitter ⚠
- p.Gly41Trp Single submitter ⚠
- p.Gly432Arg Single submitter ⚠
- p.Gly86Arg Single submitter ⚠
- p.Ile213Val Single submitter ⚠
- p.Leu303Val Single submitter ⚠
- p.Leu320Val Single submitter ⚠
- p.Leu364Phe Single submitter ⚠
- p.Leu478Phe Single submitter ⚠
- p.Leu495Phe Single submitter ⚠
- p.Leu507Phe Single submitter ⚠
- p.Lys136Thr Single submitter ⚠
- p.Lys361Glu Single submitter ⚠
- p.Lys491Arg Single submitter ⚠
- p.Met152Thr Single submitter ⚠
- p.Met506Ile Single submitter ⚠
- p.Phe177Leu Single submitter ⚠
- p.Phe317Leu Single submitter ⚠
- p.Phe518Ser Single submitter ⚠
- p.Pro215Ala Single submitter hearing loss disorder ⚠
- p.Pro494Gln Single submitter ⚠
- p.Pro509Ser Single submitter hearing loss, autosomal recessive 115 ⚠
- p.Pro71Ser Single submitter ⚠
- p.Pro71Thr Single submitter ⚠
- p.Pro72Arg Single submitter ⚠
- p.Ser172Gly Single submitter ⚠
- p.Ser319del Single submitter Inborn genetic diseases
- p.Ser51Leu Single submitter ⚠
- p.Ser96Asn Single submitter ⚠
- p.Ser96Thr Single submitter ⚠
- p.Thr228Met Single submitter ⚠
- p.Thr284Asn Single submitter ⚠
- p.Thr284Ile Single submitter ⚠
- p.Thr300Ala Single submitter ⚠
- p.Thr434Arg Single submitter ⚠
- p.Thr434Met Single submitter ⚠
- p.Thr69Pro Single submitter ⚠
- p.Thr74Pro Single submitter ⚠
- p.Thr77Pro Single submitter ⚠
- p.Trp178Ter Single submitter
- p.Trp194Arg Single submitter ⚠
- p.Val181Ile Single submitter ⚠
- p.Val233Ile Single submitter ⚠
- p.Val252Leu Single submitter ⚠
- p.Val268Leu Single submitter ⚠
- p.Val316Ile Single submitter ⚠
- p.Val399Leu Single submitter ⚠
- p.Val399Met Single submitter ⚠
- p.Val416Met Single submitter ⚠
- p.Val423Ile Single submitter ⚠
- p.Val423Leu Single submitter ⚠
- p.Val527Ile Single submitter ⚠
- p.Val64Leu Single submitter ⚠
- p.74TPG[1] No assertion criteria
- p.Asp163Asn No assertion criteria sensorineural hearing loss disorder ⚠
- p.Gly79_Cys80insThrProGly No assertion criteria SPNS2-related disorder
- p.Lys548_Val549insAlaProAlaSerValLys No assertion criteria SPNS2-related disorder