PITX2 p.Arg143=
c.429T>A · rs769461476 · VCV3046062
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
PITX2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.134 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP 0.62, phastCons 1 |
| Overall | ||
| CADD | 13.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PITX2
- Protein
- p.Arg143=
- Coding
- c.429T>A
- MANE Select
- NM_000325
- dbSNP
- rs769461476
- Type
- single nucleotide variant
- Location
- chr4:110618671 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.59 · 3 PDB
- Residue 143
- a DNA-binding region
Disease context
PITX2-related disorder
Similar variants
- PITX2 p.Arg143Pro Pathogenic ★ same residue
- PITX2 p.Arg122His Pathogenic ★★ same condition
- PITX2 c.*454C>T Benign ★★ same condition
- PITX2 p.Ser206= Benign/Likely benign ★★ same condition
- PITX2 p.Arg144Leu Likely pathogenic ★ same condition
- PITX2 p.Gln103Arg Likely pathogenic ★ same condition
- PITX2 p.Glu123Ter Likely pathogenic ★ same condition
- PITX2 p.Tyr116Ter Likely pathogenic ★ same condition
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-arg143 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown