PITX2 p.Pro211=
c.633C>T · rs2476652210 · VCV1972588
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.2e-05%)
Conditions
2
Axenfeld-Rieger syndrome type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.112 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.6 | GERP 0.64, phastCons 1 |
| Overall | ||
| CADD | 12.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.2e-05%
Overall
6.2e-05%
1/1,614,058 alleles · very rare
exomes 1/1,461,786 · genomes 0/152,272 · joint denominator
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.Pro211=
- Coding
- c.633C>T
- MANE Select
- NM_000325
- dbSNP
- rs2476652210
- Type
- single nucleotide variant
- Location
- chr4:110618467 (GRCh38)
- Gene constraint
- LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.59 · 3 PDB
- Residue 211
- a UniProt-annotated variant site (in rieg1)
Similar variants
- PITX2 p.Pro211Thr Uncertain significance ★★ ⚠ same residue
- PITX2 c.411+1G>A Pathogenic ★★ same condition
- PITX2 c.412-11A>G Pathogenic ★★ same condition
- PITX2 c.412-2A>G Pathogenic/Likely pathogenic ★★ same condition
- PITX2 p.Arg115His Pathogenic/Likely pathogenic ★★ same condition
- PITX2 p.Arg122His Pathogenic ★★ same condition
- PITX2 p.Arg144Pro Pathogenic/Likely pathogenic ★★ same condition
- PITX2 p.Arg144Trp Pathogenic/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-pro211 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown