Is ROBO2 p.Pro532= (c.1596G>A) pathogenic?

ROBO2 p.Pro532= (c.1596G>A) is classified Likely benign in ROBO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-29). Very rare (popmax 0.005%, amr); Associated with vesicoureteral reflux 2.

What condition is associated with ROBO2 p.Pro532= (c.1596G>A)?

ROBO2 p.Pro532= (c.1596G>A) is associated with vesicoureteral reflux 2 (ClinVar).

How common is ROBO2 p.Pro532= (c.1596G>A) in the general population?

ROBO2 p.Pro532= (c.1596G>A) is very rare (popmax 0.005%, amr) (gnomAD).

ROBO2 p.Pro532=

c.1596G>A · rs779025170 · VCV783310

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

vesicoureteral reflux 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.3	GERP -4.1
Overall
CADD	5.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,948 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000558% 9/1,613,556 alleles · very rare exomes 9/1,461,364 · genomes 0/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,983
South Asian	0.0011%	91,070
European (non-Finnish)	0.000424%	235,944

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: ROBO2
Protein: p.Pro532=
Coding: c.1596G>A
MANE Select: NM_001395656
dbSNP: rs779025170
Type: single nucleotide variant
Location: chr3:77563231 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78 · 6 PDB
Residue 532: the fibronectin type-iii 1 domain; a β-strand

Full ROBO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

vesicoureteral reflux 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ROBO2 p.Pro532Leu Uncertain significance ★ ⚠ same residue
ROBO2 c.1244-1G>A Uncertain significance ★★ same condition
ROBO2 c.3148+2T>C Uncertain significance ★★ same condition
ROBO2 p.Ala112Gly Uncertain significance ★★ same condition
ROBO2 p.Ala124= Uncertain significance ★★ same condition
ROBO2 p.Ala124Val Uncertain significance ★★ same condition
ROBO2 p.Ala556Thr Uncertain significance ★★ ⚠ same condition
ROBO2 p.Ala824Val Uncertain significance ★★ ⚠ 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/robo2-p-pro532 (accessed [today's date]).

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