Is ROBO2 p.Pro157= (c.471C>T) pathogenic?

ROBO2 p.Pro157= (c.471C>T) is classified Benign/Likely benign in ROBO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). Rare (popmax 0.156%, eas); Associated with vesicoureteral reflux 2.

What condition is associated with ROBO2 p.Pro157= (c.471C>T)?

ROBO2 p.Pro157= (c.471C>T) is associated with vesicoureteral reflux 2 (ClinVar).

How common is ROBO2 p.Pro157= (c.471C>T) in the general population?

ROBO2 p.Pro157= (c.471C>T) is rare (popmax 0.156%, eas) (gnomAD).

ROBO2 p.Pro157=

c.471C>T · rs201406456 · VCV346677

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.156%, eas)

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 -3.7	GERP -5.4
Overall
CADD	6.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% East Asian · 70/44,864 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0399% 644/1,613,910 alleles · rare exomes 580/1,461,778 · genomes 64/152,132 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.433%	231
East Asiangrpmax	0.156%	641
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,230
European (non-Finnish)	0.0198%	5,042
South Asian	0.0187%	5,357
African / African-American	0.004%	24,985

Finnish 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: ROBO2
Protein: p.Pro157=
Coding: c.471C>T
MANE Select: NM_001395656
dbSNP: rs201406456
Type: single nucleotide variant
Location: chr3:77477496 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78 · 6 PDB
Residue 157: an α-helix; the ig-like c2-type 2 domain

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 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
ROBO2 p.Ala872Gly 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-pro157 (accessed [today's date]).

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