Is SLIT3 p.Arg53Ser (c.157C>A) pathogenic?

SLIT3 p.Arg53Ser (c.157C>A) is classified Uncertain significance in SLIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: ambiguous (0.5405); Ultra-rare (popmax 0.0245%, nfe).

How common is SLIT3 p.Arg53Ser (c.157C>A) in the general population?

SLIT3 p.Arg53Ser (c.157C>A) is ultra-rare (popmax 0.0245%, nfe) (gnomAD).

What do computational predictors say about SLIT3 p.Arg53Ser (c.157C>A)?

AlphaMissense predicts ambiguous (score 0.5405) — an in-silico prediction, not a clinical call.

SLIT3 p.Arg53Ser

c.157C>A · rs764351814 · VCV2396235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5405 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5405	ambiguous
REVEL	0.613	indeterminate
SaProt	LLR -6.55	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	24.9	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 0.0245% European (non-Finnish) · 278/1,132,744 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0212%

Overall 0.0196% 296/1,510,198 alleles · ultra-rare exomes 283/1,358,012 · genomes 13/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0245%	4,075
Remaining individualsnot grpmax-eligible	0.0171%	5,859
Finnishnot grpmax-eligible	0.00993%	10,074
African / African-American	0.00287%	34,864
Admixed American	0.00209%	47,902

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.Arg53Ser
Coding: c.157C>A
MANE Select: NM_003062
dbSNP: rs764351814
Type: single nucleotide variant
Location: chr5:169300553 (GRCh38)
Structure: AlphaFold pLDDT 80.28
Residue 53: the lrrnt domain

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

Similar variants

SLIT3 p.Arg53Cys 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-arg53ser (accessed [today's date]).

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