Is ROBO2 p.Arg32= (c.94C>A) pathogenic?

ROBO2 p.Arg32= (c.94C>A) is classified Benign in ROBO2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Common (popmax 18.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with vesicoureteral reflux 2.

What condition is associated with ROBO2 p.Arg32= (c.94C>A)?

ROBO2 p.Arg32= (c.94C>A) is associated with vesicoureteral reflux 2 (ClinVar).

ROBO2 p.Arg32=

Q: How common is ROBO2 p.Arg32= (c.94C>A) in the general population?

ROBO2 p.Arg32= (c.94C>A) is common (popmax 18.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.94C>A · rs6788280 · VCV346675

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 18.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

vesicoureteral reflux 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.64, phastCons 0.86
Overall
CADD	10.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.6% African / African-American · 13,742/74,068 alleles

Filtering AF 18.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.2%

Overall 1.01% 16,000/1,580,932 alleles · common exomes 7,795/1,429,350 · genomes 8,205/151,582 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.6%	5
Admixed American	1.5%	67
Remaining individualsnot grpmax-eligible	1.34%	74
Middle Eastern	1.15%	87
South Asian	0.0507%	1,971
European (non-Finnish)	0.0401%	2,495

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.Arg32=
Coding: c.94C>A
MANE Select: NM_001395656
dbSNP: rs6788280
Type: single nucleotide variant
Location: chr3:77098046 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78 · 6 PDB
Residue 32: the ig-like c2-type 1 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 p.Arg32Gln 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-arg32 (accessed [today's date]).

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