Oto-palato-digital syndrome, type II: genes and variants
Oto-palato-digital syndrome, type II is linked to 1 analyzed protein (FLNA). 14 DNA variants are known to cause it; 613 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Oto-palato-digital syndrome, type I
Genes linked to Oto-palato-digital syndrome, type II
FLNA: Filamin-A
It crosslinks actin and connects the cytoskeleton to membrane receptors and signaling proteins during cell migration and tissue morphogenesis. Pathogenic variants cause a broad spectrum including periventricular nodular heterotopia and several skeletal or connective-tissue disorders.
14 disease-causing and 613 uncertain variants in FLNA are linked to Oto-palato-digital syndrome, type II.
Where Oto-palato-digital syndrome, type II variants cluster
- FLNA Calponin-homology (CH) 2 (positions 166–269): 5 of 14 disease-causing changes, 9.1× more than its size predicts.
- FLNA Filamin 10 (positions 1155–1249): 4 of 14 disease-causing changes, 8.0× more than its size predicts.
Known disease-causing variants in Oto-palato-digital syndrome, type II
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| FLNA G1576R | 1576 | Filamin 14 | Disease-causing (★★) |
| FLNA G288R | 288 | Filamin 1 | Disease-causing (★★) |
| FLNA P207L | 207 | Calponin-homology (CH) 2 | Disease-causing (★★) |
| FLNA E254K | 254 | Calponin-homology (CH) 2 | Disease-causing (★★) |
| FLNA S1186L | 1186 | Filamin 10 | Disease-causing (★★) |
| FLNA A1188T | 1188 | Filamin 10 | Disease-causing (★★) |
| FLNA S1199L | 1199 | Filamin 10 | Disease-causing (★★) |
| FLNA E82V | 82 | Calponin-homology (CH) 1 | Disease-causing (★) |
| FLNA A228S | 228 | Calponin-homology (CH) 2 | Disease-causing (★) |
| FLNA P1223L | 1223 | Filamin 10 | Disease-causing (★) |
| FLNA N94D | 94 | Calponin-homology (CH) 1 | Disease-causing (★) |
| FLNA V2644L | 2644 | Filamin 24 | Disease-causing (★) |
| FLNA D203Y | 203 | Calponin-homology (CH) 2 | Disease-causing |
| FLNA C210F | 210 | Calponin-homology (CH) 2 | Disease-causing |
Uncertain variants in Oto-palato-digital syndrome, type II that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| FLNA P207S | 207 | Calponin-homology (CH) 2 | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; P207L at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.95 |
Which prediction tools work for Oto-palato-digital syndrome, type II
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- MutPred2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 91 out of 100
- MetaLR: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 84 out of 100
- PolyPhen-2: 83 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Heterotopia, periventricular, X-linked dominant is also caused by FLNA variants; they fall mostly in different places as the Oto-palato-digital syndrome, type II variants (14 disease-causing).
- Frontometaphyseal dysplasia is also caused by FLNA variants; they fall mostly in different places as the Oto-palato-digital syndrome, type II variants (12 disease-causing).
- Melnick-Needles syndrome is also caused by FLNA variants; they fall mostly in different places as the Oto-palato-digital syndrome, type II variants (8 disease-causing).
- Cardiac valvular dysplasia, X-linked is also caused by FLNA variants; they fall mostly in different places as the Oto-palato-digital syndrome, type II variants (4 disease-causing).
Diseases related to Oto-palato-digital syndrome, type II
- Familial thoracic aortic aneurysm and aortic dissection, also linked to FLNA
- Connective tissue disorder, also linked to FLNA
- Heterotopia, periventricular, X-linked dominant, also linked to FLNA
- Frontometaphyseal dysplasia, also linked to FLNA
- Melnick-Needles syndrome, also linked to FLNA
- Periventricular nodular heterotopia, also linked to FLNA
- FG syndrome, also linked to FLNA
- Cardiac valvular dysplasia, X-linked, also linked to FLNA
Frequently asked questions
Which genes are linked to Oto-palato-digital syndrome, type II?
In CATVariant, Oto-palato-digital syndrome, type II is linked to 1 analyzed protein: FLNA (Filamin-A).
How many genetic variants are linked to Oto-palato-digital syndrome, type II?
763 variants: 14 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 613 are of uncertain significance or have conflicting reports.
Which uncertain variants in Oto-palato-digital syndrome, type II look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example FLNA P207S. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Oto-palato-digital syndrome, type II?
Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 9 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.
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