Is SLIT3 p.Pro149Arg (c.446C>G) pathogenic?

SLIT3 p.Pro149Arg (c.446C>G) is classified Uncertain significance in SLIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: likely pathogenic (0.9114); Very rare (popmax 8.47e-05%, nfe).

How common is SLIT3 p.Pro149Arg (c.446C>G) in the general population?

SLIT3 p.Pro149Arg (c.446C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SLIT3 p.Pro149Arg (c.446C>G)?

AlphaMissense predicts likely pathogenic (score 0.9114) — an in-silico prediction, not a clinical call.

SLIT3 p.Pro149Arg

c.446C>G · rs543524678 · VCV2260494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9114 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9114	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -2.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.8, phastCons 1
Overall
CADD	26.6	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 8.47e-05% European (non-Finnish) · 1/1,179,942 alleles

Overall 6.2e-05% 1/1,614,022 alleles · very rare exomes 1/1,461,762 · genomes 0/152,260 · 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: SLIT3
Protein: p.Pro149Arg
Coding: c.446C>G
MANE Select: NM_003062
dbSNP: rs543524678
Type: single nucleotide variant
Location: chr5:168883304 (GRCh38)
Structure: AlphaFold pLDDT 80.28

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

Similar variants

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
SLIT1 p.Ala437= 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-pro149arg (accessed [today's date]).

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