PITX2 p.Pro265=
c.795G>T · rs145355581 · VCV772691
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0573%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.6 | GERP -5.5 |
| Overall | ||
| CADD | 5.406 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0573%
African / African-American · 43/75,042 alleles
Filtering AF
0.0436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0389%
Overall
0.00396%
64/1,614,200 alleles · ultra-rare
exomes 33/1,461,890 · genomes 31/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0573% | 1,745 |
| Admixed American | 0.0316% | 3,160 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
| European (non-Finnish) | 8.47e-05% | 1,180,040 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PITX2
- Protein
- p.Pro265=
- Coding
- c.795G>T
- MANE Select
- NM_000325
- dbSNP
- rs145355581
- Type
- single nucleotide variant
- Location
- chr4:110618305 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.59 · 3 PDB
- Residue 265
- a UniProt-annotated variant site (in rieg1)
Similar variants
- PITX2 p.Pro265fs Pathogenic ★ same residue
- PITX2 c.411+1G>A Pathogenic ★★ same type
- PITX2 c.412-11A>G Pathogenic ★★ same type
- PITX2 c.412-2A>G Pathogenic/Likely pathogenic ★★ same type
- PITX2 p.Arg115His Pathogenic/Likely pathogenic ★★ same type
- PITX2 p.Arg122His Pathogenic ★★ same type
- PITX2 p.Arg144Pro Pathogenic/Likely pathogenic ★★ same type
- PITX2 p.Arg144Trp Pathogenic/Likely 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-pro265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown