Is PAX2 p.Pro149Ser (c.445C>T) pathogenic?

PAX2 p.Pro149Ser (c.445C>T) is classified Conflicting classifications of pathogenicity in PAX2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-14). AlphaMissense: likely benign (0.0992); Ultra-rare (popmax 0.0158%, eas); Associated with focal segmental glomerulosclerosis 7.

What condition is associated with PAX2 p.Pro149Ser (c.445C>T)?

PAX2 p.Pro149Ser (c.445C>T) is associated with focal segmental glomerulosclerosis 7, renal coloboma syndrome (ClinVar).

How common is PAX2 p.Pro149Ser (c.445C>T) in the general population?

PAX2 p.Pro149Ser (c.445C>T) is ultra-rare (popmax 0.0158%, eas) (gnomAD).

What do computational predictors say about PAX2 p.Pro149Ser (c.445C>T)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

PAX2 p.Pro149Ser

c.445C>T · rs1401507282 · VCV1475383

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

focal segmental glomerulosclerosis 7

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign
REVEL	0.563	indeterminate
SaProt	LLR -7.75	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.4 · regional, not allelic
Overall
CADD	25.6	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 0.0158% East Asian · 7/44,344 alleles

Filtering AF 0.00734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00519%

Overall 0.000501% 8/1,597,362 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0158%	6,335
European (non-Finnish)	8.53e-05%	1,172,458

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.Pro149Ser
Coding: c.445C>T
MANE Select: NM_000278
dbSNP: rs1401507282
Type: single nucleotide variant
Location: chr10:100779532 (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 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-pro149ser (accessed [today's date]).

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