RAD51AP1

Chr 12

RAD51 associated protein 1

Also known as: PIR51

RAD51AP1 encodes a structure-specific DNA-binding protein that promotes RAD51-mediated homologous recombination and DNA repair by stimulating D-loop formation and binding to branched DNA structures. Mutations cause microcephaly, growth retardation, and facial dysmorphism with autosomal recessive inheritance. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with the recessive inheritance pattern observed in affected patients.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
58
P/LP submissions
0%
P/LP missense
0.74
LOEUF
DN
Mechanism· predicted
Clinical SummaryRAD51AP1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 50 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.011
Z-score 2.32
OE 0.37 (0.200.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.47Z-score
OE missense 0.90 (0.791.03)
160 obs / 177.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.200.74)
00.351.4
Missense OE0.90 (0.791.03)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 6 / 16.0Missense obs/exp: 160 / 177.6Syn Z: 1.14
DN
0.6840th %ile
GOF
0.2994th %ile
LOF
0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

127 submitted variants in ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic5
VUS50
Likely Benign4
Benign5
53
Pathogenic
5
Likely Pathogenic
50
VUS
4
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
5
0
5
VUS
0
42
8
0
50
Likely Benign
0
4
0
0
4
Benign
0
3
1
1
5
Total049671117

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

View in ClinVar →

Protein Context — Lollipop Plot

RAD51AP1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗