Is PITX2 p.Arg96Pro (c.287_288delinsCA) pathogenic?

PITX2 p.Arg96Pro (c.287288delinsCA) is classified Uncertain significance in PITX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). Absent from gnomAD; Associated with Axenfeld-Rieger syndrome type 1.

What condition is associated with PITX2 p.Arg96Pro (c.287_288delinsCA)?

PITX2 p.Arg96Pro (c.287_288delinsCA) is associated with Axenfeld-Rieger syndrome type 1, anterior segment dysgenesis 4 (ClinVar).

How common is PITX2 p.Arg96Pro (c.287_288delinsCA) in the general population?

PITX2 p.Arg96Pro (c.287_288delinsCA) is absent from gnomAD (gnomAD).

PITX2 p.Arg96Pro

c.287_288delinsCA · rs2529773130 · VCV1998487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Axenfeld-Rieger syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.59	GERP -5.3
Regional constraint	o/e 0.28	constrained · MANE · 2,663 bp · p 1.5e-11 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PITX2
Protein: p.Arg96Pro
Coding: c.287_288delinsCA
MANE Select: NM_000325
dbSNP: rs2529773130
Type: Indel
Location: chr4:110621287 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.59 · 3 PDB
Residue 96: a DNA-binding region; the 'disordered' region; an α-helix

Full PITX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Axenfeld-Rieger syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: anterior segment dysgenesis 4

Similar variants

PITX2 p.Arg96Trp Pathogenic/Likely pathogenic ★★ same residue
PITX2 p.Tyr174_Asp175delinsTer Pathogenic ★ same condition
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

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-arg96pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown