Acne inversa, familial, 3: genes and variants
Explore variant evidence for Acne inversa, familial, 3 across 2 analyzed proteins (PSEN1, NCSTN). Linked ClinVar records include 58 pathogenic or likely pathogenic variants, 42 variants of uncertain significance and 12 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Acne inversa, familial, 3
PSEN1: Presenilin-1
Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease.
57 ClinVar pathogenic / likely pathogenic and 50 uncertain variants in PSEN1 have source records linked to Acne inversa, familial, 3. Association strength is not clinical gene validity.
NCSTN: Nicastrin
An essential subunit of the gamma-secretase complex, an intramembrane protease that processes proteins such as Notch receptors and APP. Through this complex it contributes to cell-signaling pathways and has relevance to skin disease and amyloid biology.
1 ClinVar pathogenic / likely pathogenic and 4 uncertain variants in NCSTN have source records linked to Acne inversa, familial, 3. Association strength is not clinical gene validity.
Where Acne inversa, familial, 3 variants cluster
- PSEN1 Transmembrane (positions 249–272): 10 of 57 ClinVar pathogenic / likely pathogenic variants, 3.4× more than its size predicts.
- PSEN1 Transmembrane (positions 133–153): 8 of 57 ClinVar pathogenic / likely pathogenic variants, 3.1× more than its size predicts.
- PSEN1 Transmembrane (positions 408–428): 5 of 57 ClinVar pathogenic / likely pathogenic variants, 1.9× more than its size predicts.
- PSEN1 Lumenal (positions 104–132): 6 of 57 ClinVar pathogenic / likely pathogenic variants, 1.7× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Acne inversa, familial, 3
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PSEN1 M146L | 146 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 G206A | 206 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 P267T | 267 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 P267L | 267 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 R269H | 269 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 E280G | 280 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 T116N | 116 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 P117L | 117 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 I143T | 143 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M146I | 146 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 G206D | 206 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 I249L | 249 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 R269G | 269 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A79V | 79 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 A246E | 246 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 L262V | 262 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L282P | 282 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 L113P | 113 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 Y115C | 115 | Lumenal | Pathogenic / likely pathogenic (★★) |
| PSEN1 N135S | 135 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M139K | 139 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M139V | 139 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 L271V | 271 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A431E | 431 | Required for interaction with CTNNB1 | Pathogenic / likely pathogenic (★★) |
| PSEN1 A431V | 431 | Required for interaction with CTNNB1 | Pathogenic / likely pathogenic (★★) |
| PSEN1 S169L | 169 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 F177S | 177 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 G217R | 217 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 A231T | 231 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 M233V | 233 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A285V | 285 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 L381F | 381 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 A426P | 426 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 I416T | 416 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| PSEN1 H163R | 163 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| PSEN1 T116I | 116 | Lumenal | Pathogenic / likely pathogenic (★) |
| PSEN1 P117S | 117 | Lumenal | Pathogenic / likely pathogenic (★) |
| PSEN1 I143V | 143 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 G209E | 209 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 G209V | 209 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 E280A | 280 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| PSEN1 A260V | 260 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 N135D | 135 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 I249F | 249 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 R278I | 278 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| PSEN1 V103G | 103 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 Y159F | 159 | Cytoplasmic | Pathogenic / likely pathogenic (★) |
| PSEN1 L171P | 171 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 E184D | 184 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 Q223K | 223 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 R377W | 377 | Important for cleavage of target proteins | Pathogenic / likely pathogenic (★) |
| PSEN1 L392P | 392 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 G394V | 394 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 C410Y | 410 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 L420R | 420 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 L424R | 424 | Transmembrane | Pathogenic / likely pathogenic (★) |
| PSEN1 Y256N | 256 | Transmembrane | Pathogenic / likely pathogenic (★) |
| NCSTN G33R | 33 | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Acne inversa, familial, 3
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| PSEN1 A79T | 79 | Cytoplasmic | Uncertain (★) | +6: in a 3D region that tolerates change poorly (1R); A79V at the same position is pathogenic; REVEL 0.969 |
Which prediction tools work for Acne inversa, familial, 3
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 82 out of 100
- phyloP: 78 out of 100
- CADD: 76 out of 100
Same protein, different disease
- Alzheimer disease also has ClinVar records linked to PSEN1 variants; they fall in the same places as the Acne inversa, familial, 3 variants (88 pathogenic / likely pathogenic).
- Frontotemporal dementia also has ClinVar records linked to PSEN1 variants; they fall partly in the same places as the Acne inversa, familial, 3 variants (63 pathogenic / likely pathogenic).
- Pick disease also has ClinVar records linked to PSEN1 variants; they fall in the same places as the Acne inversa, familial, 3 variants (26 pathogenic / likely pathogenic).
Diseases related to Acne inversa, familial, 3
- Telangiectasia, hereditary hemorrhagic, type 2, also linked to PSEN1
- Alzheimer disease, also linked to PSEN1
- Dilated cardiomyopathy, also linked to PSEN1
- Frontotemporal dementia, also linked to PSEN1
- Pick disease, also linked to PSEN1
- Familial isolated dilated cardiomyopathy, also linked to PSEN1
- Dementia, also linked to PSEN1
- Early-onset autosomal dominant Alzheimer disease, also linked to PSEN1
Frequently asked questions
Which genes have records linked to Acne inversa, familial, 3?
This view contains 2 analyzed proteins: PSEN1, NCSTN. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 58 pathogenic or likely pathogenic variants, 42 variants of uncertain significance and 12 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 1 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 127 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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