Is PAX2 p.Ser86Phe (c.257C>T) pathogenic?

PAX2 p.Ser86Phe (c.257C>T) is classified Uncertain significance in PAX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with focal segmental glomerulosclerosis 7.

What condition is associated with PAX2 p.Ser86Phe (c.257C>T)?

PAX2 p.Ser86Phe (c.257C>T) is associated with focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Ser86Phe (c.257C>T) in the general population?

PAX2 p.Ser86Phe (c.257C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PAX2 p.Ser86Phe (c.257C>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

PAX2 p.Ser86Phe

c.257C>T · VCV3601975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

focal segmental glomerulosclerosis 7

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 10% in PAX2
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -15.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 33 kb · p 7.6e-12 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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.Ser86Phe
Coding: c.257C>T
MANE Select: NM_000278
Type: single nucleotide variant
Location: chr10:100750738 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.52
Residue 86: a DNA-binding 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

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-ser86phe (accessed [today's date]).

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