Is SLIT3 p.Arg231Gln (c.692G>A) pathogenic?

SLIT3 p.Arg231Gln (c.692G>A) is classified Likely benign in SLIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-03). AlphaMissense: likely benign (0.2789); Rare (popmax 0.197%, amr).

How common is SLIT3 p.Arg231Gln (c.692G>A) in the general population?

SLIT3 p.Arg231Gln (c.692G>A) is rare (popmax 0.197%, amr) (gnomAD).

What do computational predictors say about SLIT3 p.Arg231Gln (c.692G>A)?

AlphaMissense predicts likely benign (score 0.2789) — an in-silico prediction, not a clinical call.

SLIT3 p.Arg231Gln

c.692G>A · rs201344625 · VCV790571

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2789 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.197%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2789	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -9.59	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% Admixed American · 118/60,030 alleles

Filtering AF 0.168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.157%

Overall 0.0147% 238/1,614,184 alleles · rare exomes 216/1,461,882 · genomes 22/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.197%	509
East Asian	0.183%	547
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0144%	6,946
African / African-American	0.004%	25,013
South Asian	0.0022%	45,543
European (non-Finnish)	0.00186%	53,638

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.Arg231Gln
Coding: c.692G>A
MANE Select: NM_003062
dbSNP: rs201344625
Type: single nucleotide variant
Location: chr5:168817401 (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

Similar variants

SLIT3 p.Arg231Ter Uncertain significance ★ same residue
SLIT3 p.Arg682Gln Uncertain significance ★★ ⚠ same type
SLIT3 p.Gly1518Ser Uncertain significance ★★ ⚠ same type
SLIT3 p.Lys1348Asn Uncertain significance ★★ ⚠ same type
SLIT3 p.Met798Thr Uncertain significance ★★ ⚠ same type
SLIT3 p.Pro1122Gln Uncertain significance ★★ ⚠ same type
SLIT3 p.Thr535Asn Uncertain significance ★★ ⚠ same type
SLIT1 c.2970-7C>T Benign ★★ 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/slit3-p-arg231gln (accessed [today's date]).

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