Is PAX2 p.Ser131= (c.393C>T) pathogenic?

PAX2 p.Ser131= (c.393C>T) is classified Likely benign in PAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-04). Very rare (popmax 0.0011%, sas); Associated with focal segmental glomerulosclerosis 7.

What condition is associated with PAX2 p.Ser131= (c.393C>T)?

PAX2 p.Ser131= (c.393C>T) is associated with focal segmental glomerulosclerosis 7, renal coloboma syndrome (ClinVar).

How common is PAX2 p.Ser131= (c.393C>T) in the general population?

PAX2 p.Ser131= (c.393C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

PAX2 p.Ser131=

c.393C>T · VCV4783633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

focal segmental glomerulosclerosis 7

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 0.031	GERP 0.4, phastCons 0.81
Overall
CADD	9.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,808 alleles · very rare exomes 3/1,461,436 · genomes 0/152,372 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,076
European (non-Finnish)	0.00017%	589,856

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.Ser131=
Coding: c.393C>T
MANE Select: NM_000278
Type: single nucleotide variant
Location: chr10:100750874 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.52
Residue 131: a DNA-binding region; the 'red subdomain' region

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 p.Ser131Arg Uncertain significance ★ ⚠ same residue
PAX2 p.Ser131Asn 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-ser131 (accessed [today's date]).

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