Is PAX2 p.Pro271Arg (c.812C>G) pathogenic?

PAX2 p.Pro271Arg (c.812C>G) is classified Uncertain significance in PAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-04). AlphaMissense: likely pathogenic (0.6153); Absent from gnomAD v4.1; Associated with focal segmental glomerulosclerosis 7.

What condition is associated with PAX2 p.Pro271Arg (c.812C>G)?

PAX2 p.Pro271Arg (c.812C>G) is associated with focal segmental glomerulosclerosis 7, renal coloboma syndrome (ClinVar).

How common is PAX2 p.Pro271Arg (c.812C>G) in the general population?

PAX2 p.Pro271Arg (c.812C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PAX2 p.Pro271Arg (c.812C>G)?

AlphaMissense predicts likely pathogenic (score 0.6153) — an in-silico prediction, not a clinical call.

PAX2 p.Pro271Arg

c.812C>G · rs2493163671 · VCV2040807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6153 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 7

Computational evidence

Protein change
AlphaMissense	0.6153	likely pathogenic
REVEL	0.82	moderately pathogenic-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.4 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P294R vs ClinVar P271R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PAX2
Protein: p.Pro271Arg
Coding: c.812C>G
MANE Select: NM_000278
dbSNP: rs2493163671
Type: single nucleotide variant
Location: chr10:100809129 (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 p.Pro271Ser Uncertain significance ★ ⚠ same residue
PAX2 p.Pro271fs Pathogenic ★ 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-pro271arg (accessed [today's date]).

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