FANCM
Chr 14ARFA complementation group M
Also known as: FAAP250, KIAA1596, POF15, SPGF28
FANCM encodes a DNA-dependent ATPase that is essential for the Fanconi anemia DNA repair pathway, processing branched DNA structures and enabling cellular resistance to DNA crosslinking damage. Biallelic mutations cause premature ovarian failure and male spermatogenic failure with autosomal recessive inheritance, representing a milder phenotype than classical Fanconi anemia. The gene is highly constrained against loss-of-function variants (LOEUF 0.59), indicating strong selection pressure.
Limited evidence — not for standalone diagnostic reporting
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 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 | 9 | 0 | 0 | 0 | 9 |
Likely Pathogenic | 3 | 0 | 0 | 0 | 3 |
VUS | 0 | 306 | 7 | 4 | 317 |
Likely Benign | 0 | 12 | 13 | 122 | 147 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 12 | 318 | 21 | 126 | 478 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FANCM · 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
A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies
RECRUITINGEvaluation of Polygenic Risk Score for Epithelial OVarian cancEr Risk Prediction: the PROVE Study
RECRUITINGExternal Resources
Links to major genomics databases and tools