Is PITX2 p.Arg115fs (c.343_364del) pathogenic?

PITX2 p.Arg115fs (c.343364del) is classified Pathogenic in PITX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2015-10-12). No gnomAD frequency available for this variant; Associated with Axenfeld-Rieger syndrome type 1.

What condition is associated with PITX2 p.Arg115fs (c.343_364del)?

PITX2 p.Arg115fs (c.343_364del) is associated with Axenfeld-Rieger syndrome type 1 (ClinVar).

How common is PITX2 p.Arg115fs (c.343_364del) in the general population?

PITX2 p.Arg115fs (c.343_364del) is no gnomAD frequency available for this variant (gnomAD).

PITX2 p.Arg115fs

c.343_364del · rs1057519483 · VCV375436

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (2 of 3, 47 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg115fs
Coding: c.343_364del
MANE Select: NM_000325
dbSNP: rs1057519483
Type: Deletion
Location: chr4:110621211 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.59 · 3 PDB
Residue 115: a DNA-binding region; a UniProt-annotated variant site (in asgd4); 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

Similar variants

PITX2 p.Arg115His Pathogenic/Likely pathogenic ★★ same residue
PITX2 p.Gln172fs Pathogenic ★★ same condition
PITX2 p.Asn168fs Pathogenic ★ same condition
PITX2 p.Asn222fs Pathogenic ★ same condition
PITX2 p.Asp175fs Pathogenic ★ same condition
PITX2 p.Ile125fs Pathogenic ★ same condition
PITX2 p.Lys89fs Pathogenic ★ same condition
PITX2 p.Ser101fs 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-arg115fs (accessed [today's date]).

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