Is SLIT3 p.Arg231Ter (c.691C>T) pathogenic?

SLIT3 p.Arg231Ter (c.691C>T) is classified Uncertain significance in SLIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-28). Very rare (popmax 0.00223%, eas); Associated with SLIT3-related anomalies of the kidney and urinary tract.

What condition is associated with SLIT3 p.Arg231Ter (c.691C>T)?

SLIT3 p.Arg231Ter (c.691C>T) is associated with SLIT3-related anomalies of the kidney and urinary tract (ClinVar).

How common is SLIT3 p.Arg231Ter (c.691C>T) in the general population?

SLIT3 p.Arg231Ter (c.691C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

SLIT3 p.Arg231Ter

c.691C>T · rs746097776 · VCV2582364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

SLIT3-related anomalies of the kidney and urinary tract

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00161% 26/1,614,064 alleles · very rare exomes 23/1,461,860 · genomes 3/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
European (non-Finnish)	0.00212%	47,201

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.Arg231Ter
Coding: c.691C>T
MANE Select: NM_003062
dbSNP: rs746097776
Type: single nucleotide variant
Location: chr5:168817402 (GRCh38)
Structure: AlphaFold pLDDT 80.28
Residue 231: the lrrct 1 domain

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

Disease context

SLIT3-related anomalies of the kidney and urinary tract

Similar variants

SLIT3 p.Arg231Gln Likely benign ★ ⚠ same residue
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.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-arg231ter (accessed [today's date]).

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