Is ROBO2 p.Pro317= (c.951C>T) pathogenic?

ROBO2 p.Pro317= (c.951C>T) is classified Likely benign in ROBO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Very rare (popmax 0.000763%, nfe).

How common is ROBO2 p.Pro317= (c.951C>T) in the general population?

ROBO2 p.Pro317= (c.951C>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

ROBO2 p.Pro317=

c.951C>T · VCV4777636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

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 0.46	GERP -3.6, phastCons 1
Overall
CADD	7.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,222 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,612,830 alleles · very rare exomes 6/1,460,870 · genomes 3/151,960 · joint denominator

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.Pro317=
Coding: c.951C>T
MANE Select: NM_001395656
Type: single nucleotide variant
Location: chr3:77546342 (GRCh38)
Gene constraint: LOEUF 0.412 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.78 · 6 PDB
Residue 317: a β-strand; the ig-like c2-type 4 domain

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

Similar variants

ROBO2 p.Pro317His Uncertain significance ★★ ⚠ same residue
ROBO2 c.1244-1G>A Uncertain significance ★★ same type
ROBO2 c.3148+2T>C Uncertain significance ★★ same type
ROBO2 p.Ala112Gly Uncertain significance ★★ same type
ROBO2 p.Ala1211Gly Uncertain significance ★★ ⚠ same type
ROBO2 p.Ala124= Uncertain significance ★★ same type
ROBO2 p.Ala124Val Uncertain significance ★★ same type
ROBO2 p.Ala556Thr Uncertain significance ★★ ⚠ same type

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-pro317 (accessed [today's date]).

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