Is PAX6 p.Pro399fs (c.1196del) pathogenic?

PAX6 p.Pro399fs (c.1196del) is classified Likely pathogenic in PAX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). No gnomAD frequency available for this variant; Associated with aniridia 1.

What condition is associated with PAX6 p.Pro399fs (c.1196del)?

PAX6 p.Pro399fs (c.1196del) is associated with aniridia 1 (ClinVar).

How common is PAX6 p.Pro399fs (c.1196del) in the general population?

PAX6 p.Pro399fs (c.1196del) is no gnomAD frequency available for this variant (gnomAD).

PAX6 p.Pro399fs

c.1196del · rs2494724434 · VCV2691816

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

aniridia 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 LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (13 of 14, 29 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 -1.9	GERP -4.2

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: PAX6
Protein: p.Pro399fs
Coding: c.1196del
MANE Select: NM_001368894
dbSNP: rs2494724434
Type: Deletion
Location: chr11:31790739 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.35 · 2 PDB
Residue 399: the 'required for suppression of nfatc1-mediated transcription' region

Full PAX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aniridia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PAX6 p.Pro399Ser Uncertain significance ★ ⚠ same residue
PAX6 c.-118_-117del Pathogenic/Likely pathogenic ★★ same condition
PAX6 c.-128-2del Pathogenic ★★ same condition
PAX6 p.Ala37fs Pathogenic ★★ same condition
PAX6 p.Gly171fs Pathogenic ★★ same condition
PAX6 p.Gly404fs Pathogenic ★★ same condition
PAX6 p.Phe15fs Pathogenic ★★ same condition
PAX6 p.Pro360fs 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/pax6-p-pro399fs (accessed [today's date]).

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