Is PAX2 p.Asp252= (c.756C>T) pathogenic?

PAX2 p.Asp252= (c.756C>T) is classified Likely benign in PAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Ultra-rare (popmax 0.0165%, mid); Associated with focal segmental glomerulosclerosis 7.

What condition is associated with PAX2 p.Asp252= (c.756C>T)?

PAX2 p.Asp252= (c.756C>T) is associated with focal segmental glomerulosclerosis 7, renal coloboma syndrome (ClinVar).

How common is PAX2 p.Asp252= (c.756C>T) in the general population?

PAX2 p.Asp252= (c.756C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PAX2 p.Asp252=

c.756C>T · rs200804078 · VCV1106175

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

focal segmental glomerulosclerosis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.674	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.003	GERP -3.7, phastCons 0.82
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000991% 16/1,614,134 alleles · ultra-rare exomes 9/1,461,782 · genomes 7/152,352 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.0107%	9,383
East Asian	0.00446%	22,438
South Asian	0.0022%	45,545
European (non-Finnish)	0.000254%	393,340

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.Asp252=
Coding: c.756C>T
MANE Select: NM_000278
dbSNP: rs200804078
Type: single nucleotide variant
Location: chr10:100806569 (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

focal segmental glomerulosclerosis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal coloboma syndrome

Similar variants

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
PAX2 p.Gly24Val Likely 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-asp252 (accessed [today's date]).

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