Is PAX6 p.Arg276Ser (c.828G>C) pathogenic?

PAX6 p.Arg276Ser (c.828G>C) is classified Pathogenic in PAX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-26). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with Peters anomaly.

What condition is associated with PAX6 p.Arg276Ser (c.828G>C)?

PAX6 p.Arg276Ser (c.828G>C) is associated with Peters anomaly (ClinVar).

How common is PAX6 p.Arg276Ser (c.828G>C) in the general population?

PAX6 p.Arg276Ser (c.828G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PAX6 p.Arg276Ser (c.828G>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

PAX6 p.Arg276Ser

c.828G>C · rs1950628459 · VCV988073

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peters anomaly

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -15.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 894 bp · p 9.1e-08 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R262S vs ClinVar R276S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PAX6
Protein: p.Arg276Ser
Coding: c.828G>C
MANE Select: NM_001368894
dbSNP: rs1950628459
Type: single nucleotide variant
Location: chr11:31793782 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.35 · 2 PDB
Residue 262 UniProt numbering: a DNA-binding 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

Similar variants

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
PAX6 c.958+1G>A Pathogenic ★★ same condition
PAX6 c.959-1G>A 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-arg276ser (accessed [today's date]).

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