RFC4 — 80 ClinVar variants

All ClinVar germline RFC4 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 61 flagged for review →

5 Pathogenic · 4 Likely pathogenic · 3 Conflicting · 1 Benign · 4 Likely benign · 63 Uncertain significance

Full RFC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions

⚑ Evidence disagreements 61

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.

RFC4 p.Glu344Lys Conflicting Single submitter
Morimoto-Ryu-Malicdan neuromuscular syndrome
RFC4 p.Leu289Arg Conflicting Single submitter
Morimoto-Ryu-Malicdan neuromuscular syndrome

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.

RFC4 c.996+2dup Conflicting Single submitter
Morimoto-Ryu-Malicdan neuromuscular syndrome

Predictors lean, ClinVar uncertain 51

ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.

Predictors split 7

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

All RFC4 variants

Pathogenic 5

p.Ala303del No assertion criteria Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Glu316fs No assertion criteria Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Ile262fs No assertion criteria Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Ile327_Thr328insIle No assertion criteria Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Val355fs No assertion criteria Morimoto-Ryu-Malicdan neuromuscular syndrome

Likely pathogenic 4

c.290+5G>T Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome
c.996+4dup Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Asp275del Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Met356fs Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome

Conflicting classifications of pathogenicity 3

c.996+2dup Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome ⚠
p.Glu344Lys Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome ⚠
p.Leu289Arg Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome ⚠

Benign 1

c.996+9G>A Multiple submitters

Likely benign 4

p.Ala271= Single submitter
p.Asn308Ser Single submitter
p.Asp137= Single submitter
p.Pro15Leu Single submitter

Uncertain significance 63

c.882+4_882+5del Single submitter
p.Ala271Val Single submitter ⚠
p.Ala279Pro Single submitter ⚠
p.Ala279Thr Single submitter ⚠
p.Ala339Glu Single submitter ⚠
p.Ala339Val Single submitter ⚠
p.Ala342Val Single submitter ⚠
p.Ala3Thr Single submitter ⚠
p.Ala53Gly Single submitter
p.Arg114His Single submitter ⚠
p.Arg135His Single submitter ⚠
p.Arg165His Single submitter ⚠
p.Arg250Gln Single submitter ⚠
p.Asn308Ile Single submitter ⚠
p.Asn317Asp Single submitter ⚠
p.Asn318Lys Single submitter ⚠
p.Asp264Gly Single submitter ⚠
p.Asp287His Single submitter ⚠
p.Asp298Asn Single submitter ⚠
p.Asp298Gly Single submitter ⚠
p.Asp343Asn Single submitter ⚠
p.Cys281Arg Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome ⚠
p.Cys281Tyr Single submitter ⚠
p.Gln128Arg Single submitter ⚠
p.Gln282Arg Single submitter ⚠
p.Gln309Glu Single submitter ⚠
p.Gln323Arg Single submitter ⚠
p.Gln358His Single submitter ⚠
p.Glu299Asp Single submitter ⚠
p.Glu31Gln Single submitter ⚠
p.Glu56Lys Single submitter ⚠
p.Gly226Arg Single submitter ⚠
p.Gly267Arg Single submitter ⚠
p.Gly276_Phe278del Single submitter
p.Gly276Glu Single submitter ⚠
p.Gly284Arg Single submitter ⚠
p.Gly300Cys Single submitter ⚠
p.Gly7Asp Single submitter ⚠
p.Ile227Thr Single submitter ⚠
p.Ile257Ser Single submitter ⚠
p.Ile269Val Single submitter ⚠
p.Ile327del Single submitter Morimoto-Ryu-Malicdan neuromuscular syndrome
p.Ile327Val Single submitter ⚠
p.Leu106Val Single submitter ⚠
p.Leu289Val Single submitter ⚠
p.Leu306His Single submitter ⚠
p.Leu66Ser Single submitter ⚠
p.Lys122Arg Single submitter ⚠
p.Phe199Leu Single submitter ⚠
p.Pro15Arg Single submitter ⚠
p.Pro15Ser Single submitter ⚠
p.Pro80Leu Single submitter ⚠
p.Ser203Leu Single submitter ⚠
p.Ser320Ala Single submitter ⚠
p.Thr82Ser Single submitter ⚠
p.Val22Gly Single submitter ⚠
p.Val22Ile Single submitter ⚠
p.Val277fs Single submitter
p.Val293Leu Single submitter ⚠
p.Val313Met Single submitter ⚠
p.Val315Leu Single submitter ⚠
p.Val334Ile Single submitter ⚠
p.Val38Ile Single submitter ⚠