Is PAX2 p.Pro161Ser (c.481C>T) pathogenic?

PAX2 p.Pro161Ser (c.481C>T) is classified Uncertain significance in PAX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0779); Very rare (popmax 0.00129%, nfe); Associated with renal coloboma syndrome.

What condition is associated with PAX2 p.Pro161Ser (c.481C>T)?

PAX2 p.Pro161Ser (c.481C>T) is associated with renal coloboma syndrome, focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Pro161Ser (c.481C>T) in the general population?

PAX2 p.Pro161Ser (c.481C>T) is very rare (popmax 0.00129%, nfe) (gnomAD).

What do computational predictors say about PAX2 p.Pro161Ser (c.481C>T)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

PAX2 p.Pro161Ser

c.481C>T · VCV3590007

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00129%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

renal coloboma syndrome

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.84, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.4 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00129% European (non-Finnish) · 15/1,167,188 alleles

Filtering AF 0.000772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000612%

Overall 0.00126% 20/1,588,226 alleles · very rare exomes 19/1,436,026 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0065%	15,393
European (non-Finnish)grpmax	0.00129%	77,813
South Asian	0.00116%	86,574

Remaining individuals 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.Pro161Ser
Coding: c.481C>T
MANE Select: NM_000278
Type: single nucleotide variant
Location: chr10:100779568 (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

renal coloboma syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: focal segmental glomerulosclerosis 7

Similar variants

PAX2 p.Pro161Leu 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
PAX2 p.Arg229Ter 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-pro161ser (accessed [today's date]).

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