RFC1

Chr 4AR

replication factor C subunit 1

Also known as: A1, CANVAS, MHCBFB, PO-GA, RECC1, RFC, RFC140

NCBI Gene: 5981ENSG00000035928UniProt: P35251OMIM: 102579

This gene encodes the large subunit of replication factor C, a five subunit DNA polymerase accessory protein, which is a DNA-dependent ATPase required for eukaryotic DNA replication and repair. The large subunit acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It may also have a role in telomere stability. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2011]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.301 OMIM phenotype
Clinical Summary— RFC1
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Gene-Disease Validity (ClinGen)
cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 149 VUS of 226 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — RFC1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.30LOEUF
pLI 0.973
Z-score 5.84
OE 0.18 (0.12–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.38Z-score
OE missense 0.84 (0.78–0.91)
502 obs / 597.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.18 (0.12–0.30)
0≤0.351.4
Missense OE?0.84 (0.78–0.91)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 11 / 59.6Missense obs/exp: 502 / 597.0Syn Z: -0.12

This gene — mechanism propensity

DN
0.3892th %ile
GOF
0.11100th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 44% of P/LP variants are LoF · LOEUF 0.30

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

226 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic3
VUS149
Likely Benign10
Benign13
13
Pathogenic
3
Likely Pathogenic
149
VUS
10
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
9
0
13
Likely Pathogenic
3
0
0
0
3
VUS
1
147
0
1
149
Likely Benign
0
4
1
5
10
Benign
0
4
5
4
13
Total81551510188

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap RFC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

RFC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients