Is SLIT3 p.Arg233= (c.699A>G) pathogenic?

SLIT3 p.Arg233= (c.699A>G) is classified Likely benign in SLIT3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-19). Rare (popmax 0.442%, sas); Associated with SLIT3-related disorder.

What condition is associated with SLIT3 p.Arg233= (c.699A>G)?

SLIT3 p.Arg233= (c.699A>G) is associated with SLIT3-related disorder (ClinVar).

How common is SLIT3 p.Arg233= (c.699A>G) in the general population?

SLIT3 p.Arg233= (c.699A>G) is rare (popmax 0.442%, sas) (gnomAD).

SLIT3 p.Arg233=

c.699A>G · rs145745913 · VCV3056199

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.442%, sas)

Conditions

SLIT3-related disorder

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 -0.51	GERP -5.5, phastCons 0.036
Overall
CADD	8.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.442% South Asian · 403/91,086 alleles

Filtering AF 0.407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.393%

Overall 0.0323% 522/1,614,196 alleles · rare exomes 484/1,461,894 · genomes 38/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.442%	226
Middle Eastern	0.181%	551
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,346
Remaining individualsnot grpmax-eligible	0.0288%	3,473
Admixed American	0.0217%	4,617
European (non-Finnish)	0.00449%	22,265
East Asian	0.00223%	44,866
African / African-American	0.00133%	75,048

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: SLIT3
Protein: p.Arg233=
Coding: c.699A>G
MANE Select: NM_003062
dbSNP: rs145745913
Type: single nucleotide variant
Location: chr5:168817394 (GRCh38)
Structure: AlphaFold pLDDT 80.28
Residue 233: the lrrct 1 domain

Full SLIT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SLIT3-related disorder

Similar variants

SLIT3 p.Arg682Gln Uncertain significance ★★ ⚠ same condition
SLIT3 p.Lys1348Asn Uncertain significance ★★ ⚠ same condition
SLIT3 p.Met798Thr Uncertain significance ★★ ⚠ same condition
SLIT3 p.Thr535Asn Uncertain significance ★★ ⚠ same condition
SLIT3 c.2483+1967A>G Uncertain significance ★ same condition
SLIT3 p.Arg231Ter Uncertain significance ★ same condition
SLIT3 p.Gln1485His Uncertain significance ★ ⚠ same condition
SLIT3 p.Arg510Cys Likely pathogenic 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/slit3-p-arg233 (accessed [today's date]).

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