Is PAX2 p.Pro173Ser (c.517C>T) pathogenic?

PAX2 p.Pro173Ser (c.517C>T) is classified Uncertain significance in PAX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.2604); Very rare (popmax 0.00133%, afr); Associated with renal coloboma syndrome.

What condition is associated with PAX2 p.Pro173Ser (c.517C>T)?

PAX2 p.Pro173Ser (c.517C>T) is associated with renal coloboma syndrome, focal segmental glomerulosclerosis 7 (ClinVar).

How common is PAX2 p.Pro173Ser (c.517C>T) in the general population?

PAX2 p.Pro173Ser (c.517C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PAX2 p.Pro173Ser (c.517C>T)?

AlphaMissense predicts likely benign (score 0.2604) — an in-silico prediction, not a clinical call.

PAX2 p.Pro173Ser

c.517C>T · VCV3590014

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal coloboma syndrome

Computational evidence

Protein change
AlphaMissense	0.2604	likely benign
REVEL	0.718	pathogenic-leaning
SaProt	LLR -6.17	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.40	acceptor gain · deltas
Pangolin	Δ0.32	gain · loss 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.4 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Overall 6.2e-05% 1/1,613,946 alleles · very rare exomes 0/1,461,726 · genomes 1/152,220 · joint denominator

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.Pro173Ser
Coding: c.517C>T
MANE Select: NM_000278
Type: single nucleotide variant
Location: chr10:100781266 (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 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-pro173ser (accessed [today's date]).

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