Is ROBO2 p.Ser802= (c.2406C>T) pathogenic?

ROBO2 p.Ser802= (c.2406C>T) is classified Benign/Likely benign in ROBO2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). Rare (popmax 0.121%, nfe); Associated with vesicoureteral reflux 2.

What condition is associated with ROBO2 p.Ser802= (c.2406C>T)?

ROBO2 p.Ser802= (c.2406C>T) is associated with vesicoureteral reflux 2 (ClinVar).

How common is ROBO2 p.Ser802= (c.2406C>T) in the general population?

ROBO2 p.Ser802= (c.2406C>T) is rare (popmax 0.121%, nfe) (gnomAD).

ROBO2 p.Ser802=

c.2406C>T · rs200412132 · VCV346699

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.121%, nfe)

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	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.048	GERP -2.5, phastCons 0.97
Overall
CADD	12.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.121% European (non-Finnish) · 1,430/1,179,654 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.0923% 1,490/1,613,496 alleles · rare exomes 1,406/1,461,446 · genomes 84/152,050 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.121%	825
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Finnishnot grpmax-eligible	0.00937%	10,671
African / African-American	0.00935%	10,696
Admixed American	0.00834%	11,992
South Asian	0.0011%	91,072

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.Ser802=
Coding: c.2406C>T
MANE Select: NM_001395656
dbSNP: rs200412132
Type: single nucleotide variant
Location: chr3:77580012 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78 · 6 PDB
Residue 802: the fibronectin type-iii 3 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-ser802 (accessed [today's date]).

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