MTRFR — 169 ClinVar variants
All ClinVar germline MTRFR variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 57 flagged for review →
13 Pathogenic · 4 Pathogenic/Likely pathogenic · 6 Likely pathogenic · 9 Conflicting · 9 Benign · 2 Benign/Likely benign · 40 Likely benign · 86 Uncertain significance
Full MTRFR gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 57
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 2
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
MTRFR p.Lys138Arg
Conflicting
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Trp159Arg
Conflicting
Single submitter
combined oxidative phosphorylation defect type 7
Predictors lean, ClinVar uncertain 44
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
MTRFR p.Ala145Thr
Uncertain significance
Multiple submitters
Spastic paraplegia
-
MTRFR p.Ala19Val
Uncertain significance
Multiple submitters
combined oxidative phosphorylation defect type 7
-
MTRFR p.Arg24Gln
Uncertain significance
Multiple submitters
combined oxidative phosphorylation defect type 7
-
MTRFR p.Arg24Leu
Uncertain significance
Multiple submitters
Spastic paraplegia
-
MTRFR p.Glu61Lys
Uncertain significance
Multiple submitters
Spastic paraplegia
-
MTRFR p.Gly71Ala
Uncertain significance
Multiple submitters
hereditary spastic paraplegia
- MTRFR p.His166Tyr Uncertain significance Multiple submitters
-
MTRFR p.Phe9Ser
Uncertain significance
Multiple submitters
Spastic paraplegia
-
MTRFR p.Pro12Ser
Uncertain significance
Multiple submitters
combined oxidative phosphorylation defect type 7
-
MTRFR p.Pro18Leu
Uncertain significance
Multiple submitters
Spastic paraplegia
-
MTRFR p.Val38Ile
Uncertain significance
Multiple submitters
combined oxidative phosphorylation defect type 7
-
MTRFR p.Val82Met
Uncertain significance
Multiple submitters
combined oxidative phosphorylation defect type 7
-
MTRFR p.Ala37Val
Uncertain significance
Single submitter
hereditary spastic paraplegia
-
MTRFR p.Arg144Lys
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
- MTRFR p.Asn124Tyr Uncertain significance Single submitter
-
MTRFR p.Asp102Asn
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Asp56His
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
- MTRFR p.Cys81Tyr Uncertain significance Single submitter
- MTRFR p.Gln113Glu Uncertain significance Single submitter
-
MTRFR p.Glu130Ala
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Glu140Gly
Uncertain significance
Single submitter
Spastic paraplegia
- MTRFR p.Gly69Ser Uncertain significance Single submitter
-
MTRFR p.Gly72Ala
Uncertain significance
Single submitter
hereditary spastic paraplegia 55
-
MTRFR p.Gly90Asp
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.His68Asn
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.His86Asp
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.His86Leu
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.His8Asp
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
- MTRFR p.Ile16Thr Uncertain significance Single submitter
-
MTRFR p.Lys137Arg
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Lys142Glu
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Lys46Glu
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Lys77Glu
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Phe64Ser
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Ser162Arg
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Ser54Pro
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Thr11Ile
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Thr14Ile
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Thr98Pro
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Val116Gly
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Val116Ile
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Val118Ala
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
- MTRFR p.Val82Leu Uncertain significance Single submitter
-
MTRFR p.Val92Ile
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
Predictors split 11
The independent predictors disagree with each other — read with care.
-
MTRFR p.Arg109Trp
Uncertain significance
Multiple submitters
combined oxidative phosphorylation defect type 7
-
MTRFR p.Arg109Gln
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Arg99Lys
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Arg99Ser
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Asn121Asp
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Gly122Ser
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
- MTRFR p.Leu158Pro Uncertain significance Single submitter
-
MTRFR p.Lys152Arg
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Lys153Asn
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
-
MTRFR p.Phe119Leu
Uncertain significance
Single submitter
Spastic paraplegia
-
MTRFR p.Val65Ala
Uncertain significance
Single submitter
combined oxidative phosphorylation defect type 7
All MTRFR variants
Pathogenic 13
- p.Arg132Ter Multiple submitters combined oxidative phosphorylation defect type 7
- p.Lys115_Val116insTer Multiple submitters C12ORF65-related disorders
- p.Pro34fs Multiple submitters C12ORF65-related disorders
- p.Pro70fs Multiple submitters combined oxidative phosphorylation defect type 7
- c.-28-1489_283-968del Single submitter neurodevelopmental disorder
- p.Asp48fs Single submitter Spastic paraplegia
- p.Gln103fs Single submitter combined oxidative phosphorylation defect type 7
- p.Lys137Ter Single submitter combined oxidative phosphorylation defect type 7
- p.Met43fs Single submitter hereditary spastic paraplegia 55
- p.Pro12fs Single submitter Spastic paraplegia
- p.Val65fs Single submitter combined oxidative phosphorylation defect type 7
- c.282+2T>A No assertion criteria hereditary spastic paraplegia 55
- p.Lys138fs No assertion criteria hereditary spastic paraplegia 55
Pathogenic/Likely pathogenic 4
- p.Arg15Ter Multiple submitters combined oxidative phosphorylation defect type 7
- p.Gly72fs Multiple submitters C12ORF65 & MTRFR-related disorders
- p.Ile87fs Multiple submitters Spastic paraplegia
- p.Val83fs Multiple submitters combined oxidative phosphorylation defect type 7
Likely pathogenic 6
- c.283-1G>T Single submitter
- p.Cys95Arg Single submitter
- p.Gln139Ter Single submitter hereditary spastic paraplegia 55
- p.Leu6fs Single submitter hereditary motor and sensory neuropathy type 6
- p.Ser89fs Single submitter combined oxidative phosphorylation defect type 7
- p.Thr148fs Single submitter
Conflicting classifications of pathogenicity 9
- p.Cys81= Single submitter combined oxidative phosphorylation defect type 7
- p.Ile111= Single submitter combined oxidative phosphorylation defect type 7
- p.Leu112= Single submitter Spastic paraplegia
- p.Lys138Arg Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Pro18= Single submitter combined oxidative phosphorylation defect type 7
- p.Thr30= Single submitter combined oxidative phosphorylation defect type 7
- p.Thr78= Single submitter hereditary spastic paraplegia
- p.Trp159Arg Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Val82= Single submitter combined oxidative phosphorylation defect type 7
Benign 9
- c.282+175A>G Multiple submitters
- c.-28-261G>T Multiple submitters
- c.-29+223C>T Multiple submitters
- c.*198T>C Multiple submitters combined oxidative phosphorylation defect type 7
- c.*483G>A Multiple submitters combined oxidative phosphorylation defect type 7
- c.*515T>G Multiple submitters combined oxidative phosphorylation defect type 7
- p.Arg15Gln Multiple submitters combined oxidative phosphorylation defect type 7
- p.Ile91= Multiple submitters combined oxidative phosphorylation defect type 7
- c.283-160A>G Single submitter
Benign/Likely benign 2
Likely benign 40
- c.283-19_283-16dup Multiple submitters combined oxidative phosphorylation defect type 7
- c.*128C>A Multiple submitters combined oxidative phosphorylation defect type 7
- c.*354G>A Multiple submitters combined oxidative phosphorylation defect type 7
- c.*454A>C Multiple submitters combined oxidative phosphorylation defect type 7
- p.Pro40= Multiple submitters Spastic paraplegia
- c.282+15G>A Single submitter combined oxidative phosphorylation defect type 7
- c.282+17C>T Single submitter combined oxidative phosphorylation defect type 7
- c.282+18G>A Single submitter combined oxidative phosphorylation defect type 7
- c.283-10T>C Single submitter Spastic paraplegia
- c.283-12_283-10del Single submitter Spastic paraplegia
- c.283-13T>C Single submitter combined oxidative phosphorylation defect type 7
- c.283-7_283-6del Single submitter Spastic paraplegia
- c.283-8T>G Single submitter Spastic paraplegia
- c.*6G>A Single submitter
- p.Ala134= Single submitter combined oxidative phosphorylation defect type 7
- p.Ala135= Single submitter combined oxidative phosphorylation defect type 7
- p.Ala19= Single submitter combined oxidative phosphorylation defect type 7
- p.Ala51= Single submitter Spastic paraplegia
- p.Arg141= Single submitter combined oxidative phosphorylation defect type 7
- p.Asn121= Single submitter
- p.Asn124= Single submitter Spastic paraplegia
- p.Glu150= Single submitter Spastic paraplegia
- p.His68= Single submitter combined oxidative phosphorylation defect type 7
- p.His86= Single submitter Spastic paraplegia
- p.Leu154= Single submitter combined oxidative phosphorylation defect type 7
- p.Leu31= Single submitter combined oxidative phosphorylation defect type 7
- p.Lys138= Single submitter
- p.Lys142= Single submitter Spastic paraplegia
- p.Lys153= Single submitter combined oxidative phosphorylation defect type 7
- p.Lys46= Single submitter combined oxidative phosphorylation defect type 7
- p.Phe119= Single submitter Spastic paraplegia
- p.Ser33= Single submitter Spastic paraplegia
- p.Ser54= Single submitter
- p.Ser89= Single submitter combined oxidative phosphorylation defect type 7
- p.Thr148= Single submitter
- p.Thr3= Single submitter combined oxidative phosphorylation defect type 7
- p.Val101= Single submitter combined oxidative phosphorylation defect type 7
- p.Val41= Single submitter combined oxidative phosphorylation defect type 7
- p.Val92= Single submitter combined oxidative phosphorylation defect type 7
- c.-8C>T No assertion criteria MTRFR-related disorder
Uncertain significance 86
- c.*439C>T Multiple submitters combined oxidative phosphorylation defect type 7
- p.Ala145Thr Multiple submitters Spastic paraplegia ⚠
- p.Ala19Val Multiple submitters combined oxidative phosphorylation defect type 7 ⚠
- p.Arg109Trp Multiple submitters combined oxidative phosphorylation defect type 7 ⚠
- p.Arg24Gln Multiple submitters combined oxidative phosphorylation defect type 7 ⚠
- p.Arg24Leu Multiple submitters Spastic paraplegia ⚠
- p.Glu61Lys Multiple submitters Spastic paraplegia ⚠
- p.Gly71Ala Multiple submitters hereditary spastic paraplegia ⚠
- p.His166Tyr Multiple submitters ⚠
- p.Phe9Ser Multiple submitters Spastic paraplegia ⚠
- p.Pro12Ser Multiple submitters combined oxidative phosphorylation defect type 7 ⚠
- p.Pro18Leu Multiple submitters Spastic paraplegia ⚠
- p.Val38Ile Multiple submitters combined oxidative phosphorylation defect type 7 ⚠
- p.Val82Met Multiple submitters combined oxidative phosphorylation defect type 7 ⚠
- c.-128C>T Single submitter combined oxidative phosphorylation defect type 7
- c.-132A>G Single submitter combined oxidative phosphorylation defect type 7
- c.-166T>C Single submitter combined oxidative phosphorylation defect type 7
- c.-206G>T Single submitter combined oxidative phosphorylation defect type 7
- c.-51C>T Single submitter combined oxidative phosphorylation defect type 7
- c.*139A>C Single submitter combined oxidative phosphorylation defect type 7
- c.*13A>C Single submitter combined oxidative phosphorylation defect type 7
- c.*143G>T Single submitter combined oxidative phosphorylation defect type 7
- c.*159G>A Single submitter combined oxidative phosphorylation defect type 7
- c.*195G>A Single submitter combined oxidative phosphorylation defect type 7
- c.*211C>T Single submitter combined oxidative phosphorylation defect type 7
- c.*212G>A Single submitter combined oxidative phosphorylation defect type 7
- c.*374A>G Single submitter combined oxidative phosphorylation defect type 7
- c.*468C>T Single submitter combined oxidative phosphorylation defect type 7
- c.*647G>C Single submitter combined oxidative phosphorylation defect type 7
- c.*674A>G Single submitter combined oxidative phosphorylation defect type 7
- c.*747G>A Single submitter combined oxidative phosphorylation defect type 7
- c.*761G>A Single submitter combined oxidative phosphorylation defect type 7
- c.*809A>C Single submitter combined oxidative phosphorylation defect type 7
- c.*853C>G Single submitter combined oxidative phosphorylation defect type 7
- c.*869T>C Single submitter combined oxidative phosphorylation defect type 7
- c.*887T>A Single submitter combined oxidative phosphorylation defect type 7
- p.Ala145fs Single submitter optic atrophy
- p.Ala37Val Single submitter hereditary spastic paraplegia ⚠
- p.Arg109Gln Single submitter Spastic paraplegia ⚠
- p.Arg144del Single submitter Spastic paraplegia
- p.Arg144Lys Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Arg99Lys Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Arg99Ser Single submitter Spastic paraplegia ⚠
- p.Asn121Asp Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Asn124del Single submitter combined oxidative phosphorylation defect type 7
- p.Asn124Tyr Single submitter ⚠
- p.Asp102Asn Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Asp56His Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Cys81Tyr Single submitter ⚠
- p.Gln113Glu Single submitter ⚠
- p.Glu130Ala Single submitter Spastic paraplegia ⚠
- p.Glu140Gly Single submitter Spastic paraplegia ⚠
- p.Gly122Ser Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Gly35Asp Single submitter combined oxidative phosphorylation defect type 7
- p.Gly69Ser Single submitter ⚠
- p.Gly72Ala Single submitter hereditary spastic paraplegia 55 ⚠
- p.Gly90Asp Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.His68Asn Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.His86Asp Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.His86Leu Single submitter Spastic paraplegia ⚠
- p.His8Asp Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Ile16Thr Single submitter ⚠
- p.Leu158Pro Single submitter ⚠
- p.Lys137Arg Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Lys142Glu Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Lys146fs Single submitter combined oxidative phosphorylation defect type 7
- p.Lys152Arg Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Lys153Asn Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Lys156fs Single submitter Spastic paraplegia
- p.Lys46Glu Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Lys47del Single submitter Spastic paraplegia
- p.Lys77Glu Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Phe119Leu Single submitter Spastic paraplegia ⚠
- p.Phe64Ser Single submitter Spastic paraplegia ⚠
- p.Ser162Arg Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Ser54Pro Single submitter Spastic paraplegia ⚠
- p.Thr11Ile Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Thr14Ile Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Thr98Pro Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Val116Ala Single submitter hereditary spastic paraplegia 55
- p.Val116Gly Single submitter Spastic paraplegia ⚠
- p.Val116Ile Single submitter Spastic paraplegia ⚠
- p.Val118Ala Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Val65Ala Single submitter combined oxidative phosphorylation defect type 7 ⚠
- p.Val82Leu Single submitter ⚠
- p.Val92Ile Single submitter combined oxidative phosphorylation defect type 7 ⚠