Sugi Variant

Sugi Variant/SPINK5

SPINK5 — 1174 ClinVar variants

All ClinVar germline SPINK5 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 385 flagged for review →

76 Pathogenic · 16 Pathogenic/Likely pathogenic · 32 Likely pathogenic · 42 Conflicting · 177 Benign · 43 Benign/Likely benign · 362 Likely benign · 426 Uncertain significance

Full SPINK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 385

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 1

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

Predictors agree, ClinVar conflicts 15

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

Predictors lean, ClinVar uncertain 243

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 243

Predictors split 126

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

All SPINK5 variants

Pathogenic 76

  • c.1302+4A>T Multiple submitters SPINK5-related disorder
  • c.2240+1G>A Multiple submitters SPINK5-related disorder
  • c.410+1G>A Multiple submitters Netherton syndrome
  • c.81+2T>A Multiple submitters ichthyosis linearis circumflexa
  • c.882+2T>C Multiple submitters Netherton syndrome
  • p.Arg217Ter Multiple submitters Netherton syndrome
  • p.Arg218Ter Multiple submitters Netherton syndrome
  • p.Arg350Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Arg371Ter Multiple submitters Netherton syndrome
  • p.Arg578Ter Multiple submitters Netherton syndrome
  • p.Arg790Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Arg853Ter Multiple submitters SPINK5-related disorder
  • p.Asp106fs Multiple submitters SPINK5-related disorder
  • p.Cys239fs Multiple submitters ichthyosis linearis circumflexa
  • p.Cys510Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Gln334Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Gly700Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Leu132fs Multiple submitters Netherton syndrome
  • p.Leu591fs Multiple submitters ichthyosis linearis circumflexa
  • p.Lys754Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Lys823fs Multiple submitters ichthyosis linearis circumflexa
  • p.Lys824fs Multiple submitters ichthyosis linearis circumflexa
  • p.Lys860fs Multiple submitters ichthyosis linearis circumflexa
  • p.Tyr363Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Tyr874Ter Multiple submitters ichthyosis linearis circumflexa
  • c.1816_1820+21delinsCT Single submitter Netherton syndrome
  • c.1888-1G>A Single submitter ichthyosis linearis circumflexa
  • c.2667-1G>A Single submitter
  • c.410+1G>T Single submitter Netherton syndrome
  • c.666+1G>C Single submitter Netherton syndrome
  • c.666+1G>T Single submitter ichthyosis linearis circumflexa
  • c.882+1_882+3del Single submitter Netherton syndrome
  • p.Arg857Ter Single submitter ichthyosis linearis circumflexa
  • p.Asp277fs Single submitter ichthyosis linearis circumflexa
  • p.Asp828fs Single submitter ichthyosis linearis circumflexa
  • p.Cys119_Lys124delinsAspAsnIleTer Single submitter ichthyosis linearis circumflexa
  • p.Cys15Ter Single submitter ichthyosis linearis circumflexa
  • p.Gln338Ter Single submitter ichthyosis linearis circumflexa
  • p.Gln46Ter Single submitter
  • p.Gln52fs Single submitter Netherton syndrome
  • p.Gln564Ter Single submitter ichthyosis linearis circumflexa
  • p.Gln609Ter Single submitter ichthyosis linearis circumflexa
  • p.Gln739Ter Single submitter
  • p.Glu227Ter Single submitter ichthyosis linearis circumflexa
  • p.Glu314fs Single submitter
  • p.Glu412fs Single submitter ichthyosis linearis circumflexa
  • p.Glu480fs Single submitter ichthyosis linearis circumflexa
  • p.Glu539fs Single submitter
  • p.Glu71Ter Single submitter ichthyosis linearis circumflexa
  • p.Glu73fs Single submitter ichthyosis linearis circumflexa
  • p.Glu776fs Single submitter
  • p.Glu820fs Single submitter ichthyosis linearis circumflexa
  • p.Glu825fs Single submitter ichthyosis linearis circumflexa
  • p.Glu968fs Single submitter
  • p.Gly447Ter Single submitter ichthyosis linearis circumflexa
  • p.Ile509fs Single submitter Netherton syndrome
  • p.Leu639fs Single submitter ichthyosis linearis circumflexa
  • p.Lys230fs Single submitter ichthyosis linearis circumflexa
  • p.Lys23Ter Single submitter ichthyosis linearis circumflexa
  • p.Lys415fs Single submitter ichthyosis linearis circumflexa
  • p.Lys680fs Single submitter ichthyosis linearis circumflexa
  • p.Lys823Ter Single submitter
  • p.Met951fs Single submitter ichthyosis linearis circumflexa
  • p.Phe43fs Single submitter ichthyosis linearis circumflexa
  • p.Phe985fs Single submitter ichthyosis linearis circumflexa
  • p.Ser909Ter Single submitter ichthyosis linearis circumflexa
  • p.Thr125fs Single submitter ichthyosis linearis circumflexa
  • p.Thr808del Single submitter ichthyosis linearis circumflexa
  • p.Tyr1004fs Single submitter ichthyosis linearis circumflexa
  • p.Tyr228Ter Single submitter ichthyosis linearis circumflexa
  • p.Tyr440Ter Single submitter Netherton syndrome
  • p.Val160fs Single submitter ichthyosis linearis circumflexa
  • p.Val232fs Single submitter ichthyosis linearis circumflexa
  • c.283-2A>T No assertion criteria Netherton syndrome
  • p.Cys119fs No assertion criteria Netherton syndrome
  • p.Met332fs No assertion criteria Netherton syndrome

Pathogenic/Likely pathogenic 16

  • c.1430+1G>T Multiple submitters ichthyosis linearis circumflexa
  • c.1431-12G>A Multiple submitters SPINK5-related disorder
  • c.666+1G>A Multiple submitters ichthyosis linearis circumflexa
  • c.81+5G>A Multiple submitters ichthyosis linearis circumflexa
  • p.Ala80fs Multiple submitters ichthyosis linearis circumflexa
  • p.Arg210Ter Multiple submitters Netherton syndrome
  • p.Arg871Ter Multiple submitters SPINK5-related disorder
  • p.Arg891Ter Multiple submitters SPINK5-related disorder
  • p.Arg920Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Arg997Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Cys1006Ter Multiple submitters ichthyosis linearis circumflexa
  • p.Cys297= Multiple submitters ichthyosis linearis circumflexa
  • p.Gln231fs Multiple submitters SPINK5-related disorder
  • p.Glu284fs Multiple submitters ichthyosis linearis circumflexa
  • p.Leu957fs Multiple submitters ichthyosis linearis circumflexa
  • p.Thr808Ile Multiple submitters ichthyosis linearis circumflexa ⚠

Likely pathogenic 32

Conflicting classifications of pathogenicity 42

Benign 177

Benign/Likely benign 43

  • c.1011-12C>T Multiple submitters Netherton syndrome
  • c.1093-10A>G Multiple submitters Netherton syndrome
  • c.1302+16C>T Multiple submitters ichthyosis linearis circumflexa
  • c.1302+19G>A Multiple submitters Netherton syndrome
  • c.209+15C>T Multiple submitters Netherton syndrome
  • c.2113-18G>A Multiple submitters ichthyosis linearis circumflexa
  • c.2241-6C>T Multiple submitters ichthyosis linearis circumflexa
  • c.2442-16A>G Multiple submitters ichthyosis linearis circumflexa
  • c.2538+18C>T Multiple submitters ichthyosis linearis circumflexa
  • c.2667-12del Multiple submitters ichthyosis linearis circumflexa
  • c.2667-13delinsTT Multiple submitters
  • c.2667-4G>A Multiple submitters ichthyosis linearis circumflexa
  • c.2740-170G>A Multiple submitters
  • c.3186+8C>T Multiple submitters Netherton syndrome
  • c.882+20A>G Multiple submitters Netherton syndrome
  • p.Ala335Val Multiple submitters ichthyosis linearis circumflexa
  • p.Ala617= Multiple submitters ichthyosis linearis circumflexa
  • p.Arg268Cys Multiple submitters Netherton syndrome ⚠
  • p.Arg711Gln Multiple submitters Netherton syndrome
  • p.Asn376= Multiple submitters Netherton syndrome
  • p.Asn921Ser Multiple submitters ichthyosis linearis circumflexa
  • p.Asp106Asn Multiple submitters ichthyosis linearis circumflexa
  • p.Asp386Asn Multiple submitters ichthyosis linearis circumflexa
  • p.Gln267Arg Multiple submitters ichthyosis linearis circumflexa
  • p.Gln687= Multiple submitters ichthyosis linearis circumflexa
  • p.Glu825Asp Multiple submitters ichthyosis linearis circumflexa
  • p.Glu918= Multiple submitters ichthyosis linearis circumflexa
  • p.Gly1003= Multiple submitters Netherton syndrome
  • p.Gly40Ala Multiple submitters ichthyosis linearis circumflexa ⚠
  • p.Gly463= Multiple submitters Netherton syndrome
  • p.Gly804= Multiple submitters Netherton syndrome
  • p.His396= Multiple submitters ichthyosis linearis circumflexa
  • p.His972Arg Multiple submitters ichthyosis linearis circumflexa
  • p.Leu16= Multiple submitters ichthyosis linearis circumflexa
  • p.Leu786= Multiple submitters Netherton syndrome
  • p.Lys420Glu Multiple submitters ichthyosis linearis circumflexa
  • p.Lys969Glu Multiple submitters ichthyosis linearis circumflexa
  • p.Pro1061= Multiple submitters ichthyosis linearis circumflexa
  • p.Pro794= Multiple submitters ichthyosis linearis circumflexa
  • p.Ser368Asn Multiple submitters Netherton syndrome
  • p.Ser887Arg Multiple submitters ichthyosis linearis circumflexa ⚠
  • p.Val246= Multiple submitters Netherton syndrome
  • p.Val553= Multiple submitters ichthyosis linearis circumflexa

Likely benign 362

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

Uncertain significance 426

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