Is PAX2 p.Ala91= (c.273G>A) pathogenic?

PAX2 p.Ala91= (c.273G>A) is classified Likely benign in PAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). Very rare (popmax 0.00534%, afr); Associated with renal coloboma syndrome.

What condition is associated with PAX2 p.Ala91= (c.273G>A)?

PAX2 p.Ala91= (c.273G>A) is associated with renal coloboma syndrome, focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Ala91= (c.273G>A) in the general population?

PAX2 p.Ala91= (c.273G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

PAX2 p.Ala91=

c.273G>A · rs769483204 · VCV2161712

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

renal coloboma syndrome

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 -1.2	GERP -5.2
Overall
CADD	4.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,940 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000496% 8/1,614,078 alleles · very rare exomes 6/1,461,854 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,735
Admixed American	0.00167%	60,014
European (non-Finnish)	0.000254%	393,343

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: PAX2
Protein: p.Ala91=
Coding: c.273G>A
MANE Select: NM_000278
dbSNP: rs769483204
Type: single nucleotide variant
Location: chr10:100750754 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.52
Residue 91: a DNA-binding region

Full PAX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal coloboma syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 7

Similar variants

PAX2 p.Ala91Val Uncertain significance ★ ⚠ same residue
PAX2 c.212+1G>T Pathogenic/Likely pathogenic ★★ same condition
PAX2 c.213-8C>A Likely pathogenic ★★ same condition
PAX2 c.792+2T>C Pathogenic ★★ same condition
PAX2 p.Arg104Ter Pathogenic ★★ same condition
PAX2 p.Arg115Ter Pathogenic ★★ same condition
PAX2 p.Arg140Trp Pathogenic ★★ same condition
PAX2 p.Arg229Ter 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/pax2-p-ala91 (accessed [today's date]).

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