Is PAX6 p.Pro90= (c.270G>A) pathogenic?

PAX6 p.Pro90= (c.270G>A) is classified Likely benign in PAX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). Very rare (popmax 8.47e-05%, nfe); Associated with Peters anomaly.

What condition is associated with PAX6 p.Pro90= (c.270G>A)?

PAX6 p.Pro90= (c.270G>A) is associated with Peters anomaly, aniridia 1 (ClinVar).

How common is PAX6 p.Pro90= (c.270G>A) in the general population?

PAX6 p.Pro90= (c.270G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PAX6 p.Pro90=

c.270G>A · rs962179691 · VCV2921397

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Peters anomaly

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 -5.1	GERP -4.2
Overall
CADD	5.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 6.2e-05% 1/1,614,058 alleles · very rare exomes 0/1,461,894 · genomes 1/152,164 · 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: PAX6
Protein: p.Pro90=
Coding: c.270G>A
MANE Select: NM_001368894
dbSNP: rs962179691
Type: single nucleotide variant
Location: chr11:31801690 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.35 · 2 PDB
Residue 90: a DNA-binding region; the 'red subdomain' region; an α-helix

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

Disease context

Peters anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aniridia 1

Similar variants

PAX6 p.Pro90Leu Likely pathogenic ★ same residue
PAX6 p.Pro90Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
PAX6 c.1074+1G>C Pathogenic ★★ same condition
PAX6 c.1075-2A>G Pathogenic ★★ same condition
PAX6 c.1225+5G>A Pathogenic/Likely pathogenic ★★ same condition
PAX6 c.141+1G>A Pathogenic ★★ same condition
PAX6 c.399+1G>A Pathogenic ★★ same condition
PAX6 c.399+1G>C 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-pro90 (accessed [today's date]).

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