Telangiectasia, hereditary hemorrhagic, type 2: genes and variants
Telangiectasia, hereditary hemorrhagic, type 2 is linked to 2 analyzed proteins (ACVRL1 and PSEN1). 179 DNA variants are known to cause it; 154 more are uncertain, and 17 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: telangiectasia, hereditary hemorrhagic, type 1
Genes linked to Telangiectasia, hereditary hemorrhagic, type 2
ACVRL1: Activin receptor type-1-like
It mediates BMP9 and BMP10 signaling in vascular endothelial cells and helps maintain normal vessel maturation and quiescence. Heterozygous loss-of-function variants cause hereditary hemorrhagic telangiectasia type 2, with telangiectasias and arteriovenous malformations.
178 disease-causing and 154 uncertain variants in ACVRL1 are linked to Telangiectasia, hereditary hemorrhagic, type 2.
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.
1 disease-causing and 0 uncertain variants in PSEN1 are linked to Telangiectasia, hereditary hemorrhagic, type 2.
Known disease-causing variants in Telangiectasia, hereditary hemorrhagic, type 2
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ACVRL1 C89F | 89 | Extracellular | Disease-causing (★★★) |
| ACVRL1 R411Q | 411 | Protein kinase | Disease-causing (★★★) |
| ACVRL1 C51G | 51 | Extracellular | Disease-causing (★★★) |
| ACVRL1 H328Y | 328 | Protein kinase | Disease-causing (★★★) |
| ACVRL1 S333I | 333 | Protein kinase | Disease-causing (★★★) |
| ACVRL1 C46S | 46 | Extracellular | Disease-causing (★★★) |
| ACVRL1 S186I | 186 | GS | Disease-causing (★★★) |
| ACVRL1 N98S | 98 | Extracellular | Disease-causing (★★★) |
| ACVRL1 E236K | 236 | Protein kinase | Disease-causing (★★★) |
| ACVRL1 C69F | 69 | Extracellular | Disease-causing (★★) |
| ACVRL1 G211D | 211 | Protein kinase | Disease-causing (★★) |
| ACVRL1 C344Y | 344 | Protein kinase | Disease-causing (★★) |
| ACVRL1 A352D | 352 | Protein kinase | Disease-causing (★★) |
| ACVRL1 E379K | 379 | Protein kinase | Disease-causing (★★) |
| ACVRL1 R411W | 411 | Protein kinase | Disease-causing (★★) |
| ACVRL1 G48E | 48 | Extracellular | Disease-causing (★★) |
| ACVRL1 C51Y | 51 | Extracellular | Disease-causing (★★) |
| ACVRL1 C51S | 51 | Extracellular | Disease-causing (★★) |
| ACVRL1 R67W | 67 | Extracellular | Disease-causing (★★) |
| ACVRL1 C69R | 69 | Extracellular | Disease-causing (★★) |
| ACVRL1 C89R | 89 | Extracellular | Disease-causing (★★) |
| ACVRL1 C90F | 90 | Extracellular | Disease-causing (★★) |
| ACVRL1 C90Y | 90 | Extracellular | Disease-causing (★★) |
| ACVRL1 N96D | 96 | Extracellular | Disease-causing (★★) |
| ACVRL1 T277K | 277 | Protein kinase | Disease-causing (★★) |
| ACVRL1 T277R | 277 | Protein kinase | Disease-causing (★★) |
| ACVRL1 G309S | 309 | Protein kinase | Disease-causing (★★) |
| ACVRL1 H314Y | 314 | Protein kinase | Disease-causing (★★) |
| ACVRL1 H328P | 328 | Protein kinase | Disease-causing (★★) |
| ACVRL1 C344F | 344 | Protein kinase | Disease-causing (★★) |
| ACVRL1 C344R | 344 | Protein kinase | Disease-causing (★★) |
| ACVRL1 G350R | 350 | Protein kinase | Disease-causing (★★) |
| ACVRL1 G350S | 350 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P378S | 378 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P378L | 378 | Protein kinase | Disease-causing (★★) |
| ACVRL1 D397N | 397 | Protein kinase | Disease-causing (★★) |
| ACVRL1 W399G | 399 | Protein kinase | Disease-causing (★★) |
| ACVRL1 W399S | 399 | Protein kinase | Disease-causing (★★) |
| ACVRL1 A400D | 400 | Protein kinase | Disease-causing (★★) |
| ACVRL1 A400V | 400 | Protein kinase | Disease-causing (★★) |
| ACVRL1 A400P | 400 | Protein kinase | Disease-causing (★★) |
| ACVRL1 A400T | 400 | Protein kinase | Disease-causing (★★) |
| ACVRL1 E407D | 407 | Protein kinase | Disease-causing (★★) |
| ACVRL1 E407K | 407 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P424R | 424 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P424S | 424 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P449L | 449 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P476L | 476 | Protein kinase | Disease-causing (★★) |
| ACVRL1 P476R | 476 | Protein kinase | Disease-causing (★★) |
| ACVRL1 R479Q | 479 | Protein kinase | Disease-causing (★★) |
| ACVRL1 R484L | 484 | Protein kinase | Disease-causing (★★) |
| ACVRL1 R484P | 484 | Protein kinase | Disease-causing (★★) |
| ACVRL1 C34Y | 34 | Extracellular | Disease-causing (★★) |
| ACVRL1 W50C | 50 | Extracellular | Disease-causing (★★) |
| ACVRL1 W50R | 50 | Extracellular | Disease-causing (★★) |
| ACVRL1 R67G | 67 | Extracellular | Disease-causing (★★) |
| ACVRL1 C77R | 77 | Extracellular | Disease-causing (★★) |
| ACVRL1 C90W | 90 | Extracellular | Disease-causing (★★) |
| ACVRL1 N96S | 96 | Extracellular | Disease-causing (★★) |
| ACVRL1 L273P | 273 | Protein kinase | Disease-causing (★★) |
Showing 60 of 179.
Uncertain variants in Telangiectasia, hereditary hemorrhagic, type 2 that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ACVRL1 P433L | 433 | Protein kinase | Conflicting reports (★) | +7: 2 other pathogenic changes within 3 positions; P433S at the same position is pathogenic; seen in 6.8e-07 of gnomAD DNA copies; REVEL 0.931 |
| ACVRL1 N335S | 335 | Protein kinase | Conflicting reports (★) | +7: 7 other pathogenic changes within 3 positions; N335I at the same position is pathogenic; seen in 6.9e-07 of gnomAD DNA copies; REVEL 0.866 |
| ACVRL1 R200Q | 200 | GS | Uncertain (★★) | +7: 2 other pathogenic changes within 3 positions; R200G at the same position is pathogenic; seen in 7.5e-06 of gnomAD DNA copies; REVEL 0.775 |
| ACVRL1 L337P | 337 | Protein kinase | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; L337R at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 Y375N | 375 | Protein kinase | Conflicting reports (★) | +6: 12 other pathogenic changes within 3 positions; Y375F at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 Y375C | 375 | Protein kinase | Conflicting reports (★) | +6: 12 other pathogenic changes within 3 positions; Y375F at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 T197K | 197 | GS | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; T197I at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
| ACVRL1 D348N | 348 | Protein kinase | Conflicting reports (★) | +6: 7 other pathogenic changes within 3 positions; D348H at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 A327P | 327 | Protein kinase | Conflicting reports (★) | +6: 7 other pathogenic changes within 3 positions; A327D at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 R200W | 200 | GS | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R200G at the same position is pathogenic; REVEL 0.914 |
| ACVRL1 V442M | 442 | Protein kinase | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; V442A at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.90 |
| ACVRL1 E379Q | 379 | Protein kinase | Uncertain (★) | +6: 11 other pathogenic changes within 3 positions; E379K at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
| ACVRL1 H328Q | 328 | Protein kinase | Uncertain (★) | +6: 8 other pathogenic changes within 3 positions; H328P at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 C471Y | 471 | Protein kinase | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; C471G at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
| ACVRL1 A482T | 482 | Protein kinase | Uncertain (★) | +6: 7 other pathogenic changes within 3 positions; A482E at the same position is pathogenic; seen in 8.9e-06 of gnomAD DNA copies; REVEL 0.717 |
| ACVRL1 T271R | 271 | Protein kinase | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; T271K at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| ACVRL1 K487E | 487 | Protein kinase | Uncertain (★) | +6: 4 other pathogenic changes within 3 positions; K487T at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.99 |
Which prediction tools work for Telangiectasia, hereditary hemorrhagic, type 2
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 86 out of 100
- CADD: 82 out of 100
- REVEL: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 73 out of 100
Same protein, different disease
- Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia is also caused by ACVRL1 variants; they fall in the same places as the Telangiectasia, hereditary hemorrhagic, type 2 variants (6 disease-causing).
- Pulmonary hypertension, primary, 1 is also caused by ACVRL1 variants; they fall in the same places as the Telangiectasia, hereditary hemorrhagic, type 2 variants (3 disease-causing).
- Alzheimer disease is also caused by PSEN1 variants; they fall mostly in different places as the Telangiectasia, hereditary hemorrhagic, type 2 variants (88 disease-causing).
- Frontotemporal dementia is also caused by PSEN1 variants; they fall mostly in different places as the Telangiectasia, hereditary hemorrhagic, type 2 variants (63 disease-causing).
- Acne inversa, familial, 3 is also caused by PSEN1 variants; they fall mostly in different places as the Telangiectasia, hereditary hemorrhagic, type 2 variants (57 disease-causing).
- Pick disease is also caused by PSEN1 variants; they fall mostly in different places as the Telangiectasia, hereditary hemorrhagic, type 2 variants (26 disease-causing).
Diseases related to Telangiectasia, hereditary hemorrhagic, type 2
- Hereditary factor VIII deficiency disease, also linked to ACVRL1
- Alzheimer disease, also linked to PSEN1
- Dilated cardiomyopathy, also linked to PSEN1
- Frontotemporal dementia, also linked to PSEN1
- Acne inversa, familial, 3, also linked to PSEN1
- Pulmonary hypertension, primary, 1, also linked to ACVRL1
- Pulmonary arterial hypertension, also linked to ACVRL1
- Pick disease, also linked to PSEN1
- Pulmonary arterial hypertension related to hereditary hemorrhagic telangiectasia, also linked to ACVRL1
- Hereditary hemorrhagic telangiectasia, also linked to ACVRL1
- Familial isolated dilated cardiomyopathy, also linked to PSEN1
- Dementia, also linked to PSEN1
Frequently asked questions
Which genes are linked to Telangiectasia, hereditary hemorrhagic, type 2?
In CATVariant, Telangiectasia, hereditary hemorrhagic, type 2 is linked to 2 analyzed proteins: ACVRL1 (Activin receptor type-1-like) and PSEN1 (Presenilin-1).
How many genetic variants are linked to Telangiectasia, hereditary hemorrhagic, type 2?
395 variants: 179 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 154 are of uncertain significance or have conflicting reports.
Which uncertain variants in Telangiectasia, hereditary hemorrhagic, type 2 look disease-causing?
17 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ACVRL1 P433L, ACVRL1 N335S, ACVRL1 R200Q, ACVRL1 L337P and ACVRL1 Y375N. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Telangiectasia, hereditary hemorrhagic, type 2?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.86, based on 152 disease-causing and 16 harmless variants).
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center