RFC5
Chr 12replication factor C subunit 5
Also known as: RFC36
The RFC5 protein is the smallest subunit of the replication factor C complex, which loads proliferating cell nuclear antigen onto DNA during replication and is required for DNA synthesis by polymerases delta and epsilon. Mutations cause autosomal recessive Neurofibromatosis-like syndrome, characterized by café-au-lait spots, learning disabilities, and dysmorphic features. The gene shows low constraint to loss-of-function variation (pLI 0.0005, LOEUF 0.75), suggesting tolerance to reduced gene dosage.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 3 | 0 | 4 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 1 | 51 | 2 | 0 | 54 |
Likely Benign | 0 | 1 | 0 | 2 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 1 | 53 | 9 | 2 | 65 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RFC5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools