Is PAX2 p.Arg40= (c.120C>T) pathogenic?

PAX2 p.Arg40= (c.120C>T) is classified Likely benign in PAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Very rare (popmax 0.000254%, nfe); Associated with renal coloboma syndrome.

What condition is associated with PAX2 p.Arg40= (c.120C>T)?

PAX2 p.Arg40= (c.120C>T) is associated with renal coloboma syndrome, focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Arg40= (c.120C>T) in the general population?

PAX2 p.Arg40= (c.120C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

PAX2 p.Arg40=

c.120C>T · rs747639516 · VCV1437935

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 4.8	GERP 1.5, phastCons 1
Overall
CADD	16.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,178,982 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,706 alleles · very rare

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.Arg40=
Coding: c.120C>T
MANE Select: NM_000278
dbSNP: rs747639516
Type: single nucleotide variant
Location: chr10:100749822 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.52
Residue 40: a DNA-binding region; a UniProt-annotated variant site (in paprs; the patient manifests oligomeganephronia and bilateral optic nerve coloboma); the 'pai subdomain' 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.Arg40_Ile41insGlnArg Uncertain significance ★ same residue
PAX2 p.Arg40Cys 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

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-arg40 (accessed [today's date]).

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