PITX2 p.Pro117fs
c.350del · VCV4796478
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Axenfeld-Rieger syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 3 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.63 | GERP -5.3, phastCons 0.021 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PITX2
- Protein
- p.Pro117fs
- Coding
- c.350del
- MANE Select
- NM_000325
- Type
- Deletion
- Location
- chr4:110621225 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.59 · 3 PDB
- Residue 117
- a DNA-binding region; an α-helix
Similar variants
- PITX2 p.Pro117Arg Pathogenic ★ same residue
- PITX2 p.Pro117Leu Pathogenic same residue
- PITX2 p.Gln172fs Pathogenic ★★ same type
- PITX2 p.Tyr280fs Pathogenic/Likely pathogenic ★★ same type
- PITX2 p.Ala187fs Likely pathogenic ★ same type
- PITX2 p.Asn168fs Pathogenic ★ same type
- PITX2 p.Asn222fs Pathogenic ★ same type
- PITX2 p.Asp175fs Pathogenic ★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pitx2-p-pro117fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown