Is PAX2 p.Pro366Ser (c.1096C>T) pathogenic?

PAX2 p.Pro366Ser (c.1096C>T) is classified Conflicting classifications of pathogenicity in PAX2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-05). AlphaMissense: likely benign (0.2529); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with PAX2 p.Pro366Ser (c.1096C>T)?

PAX2 p.Pro366Ser (c.1096C>T) is associated with Inborn genetic diseases, renal coloboma syndrome, focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Pro366Ser (c.1096C>T) in the general population?

PAX2 p.Pro366Ser (c.1096C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PAX2 p.Pro366Ser (c.1096C>T)?

AlphaMissense predicts likely benign (score 0.2529) — an in-silico prediction, not a clinical call.

PAX2 p.Pro366Ser

c.1096C>T · rs1317595421 · VCV3208972

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2529	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.4 · regional, not allelic
Overall
CADD	26.4	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 P389S vs ClinVar P366S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,868 alleles

Overall 0.000137% 2/1,460,530 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,576
East Asiangrpmax	0.00223%	44,868

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro366Ser
Coding: c.1096C>T
MANE Select: NM_000278
dbSNP: rs1317595421
Type: single nucleotide variant
Location: chr10:100827083 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal coloboma syndrome focal segmental glomerulosclerosis 7

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-pro366ser (accessed [today's date]).

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