Is PAX2 p.Ser282= (c.846G>A) pathogenic?

PAX2 p.Ser282= (c.846G>A) is classified Benign/Likely benign in PAX2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-11-22). Ultra-rare (popmax 0.0334%, eas); Associated with renal coloboma syndrome.

What condition is associated with PAX2 p.Ser282= (c.846G>A)?

PAX2 p.Ser282= (c.846G>A) is associated with renal coloboma syndrome, focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Ser282= (c.846G>A) in the general population?

PAX2 p.Ser282= (c.846G>A) is ultra-rare (popmax 0.0334%, eas) (gnomAD).

PAX2 p.Ser282=

c.846G>A · rs777494044 · VCV1950039

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, eas)

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 -3.1	GERP -3.5
Overall
CADD	1.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% East Asian · 15/44,882 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.00192% 31/1,612,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0334%	2,992
Remaining individualsnot grpmax-eligible	0.0048%	20,816
Admixed American	0.00167%	59,990
African / African-American	0.00134%	74,872
South Asian	0.0011%	91,050
European (non-Finnish)	0.000848%	117,911

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.Ser282=
Coding: c.846G>A
MANE Select: NM_000278
dbSNP: rs777494044
Type: single nucleotide variant
Location: chr10:100809163 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.52

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.Ser282Ter Likely pathogenic ★ same residue
PAX2 p.Ser282Leu Conflicting classifications of pathogenicity ★ ⚠ 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

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-ser282 (accessed [today's date]).

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