Is SLIT3 p.Pro997= (c.2991A>G) pathogenic?

SLIT3 p.Pro997= (c.2991A>G) is classified Likely benign in SLIT3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-06). Ultra-rare (popmax 0.0367%, amr); Associated with SLIT3-related disorder.

What condition is associated with SLIT3 p.Pro997= (c.2991A>G)?

SLIT3 p.Pro997= (c.2991A>G) is associated with SLIT3-related disorder (ClinVar).

How common is SLIT3 p.Pro997= (c.2991A>G) in the general population?

SLIT3 p.Pro997= (c.2991A>G) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

SLIT3 p.Pro997=

c.2991A>G · rs1454938390 · VCV3029294

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

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 -7	GERP -4.2
Overall
CADD	0.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0367% Admixed American · 22/60,002 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00149% 24/1,614,070 alleles · ultra-rare exomes 7/1,461,888 · genomes 17/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,727
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,920

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.Pro997=
Coding: c.2991A>G
MANE Select: NM_003062
dbSNP: rs1454938390
Type: single nucleotide variant
Location: chr5:168696383 (GRCh38)
Structure: AlphaFold pLDDT 80.28
Residue 997: the egf-like 2 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-pro997 (accessed [today's date]).

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