Is SLIT3 p.Ser488= (c.1464C>T) pathogenic?

SLIT3 p.Ser488= (c.1464C>T) is classified Likely benign in SLIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Very rare (popmax 0.00988%, sas).

How common is SLIT3 p.Ser488= (c.1464C>T) in the general population?

SLIT3 p.Ser488= (c.1464C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

SLIT3 p.Ser488=

c.1464C>T · rs774418931 · VCV2656061

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

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 -7.4	GERP -5.5
Overall
CADD	2.293	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00988% South Asian · 9/91,076 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00291% 47/1,613,208 alleles · very rare exomes 37/1,461,048 · genomes 10/152,160 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0361%	2,770
South Asiangrpmax	0.00988%	10,120
East Asian	0.00446%	22,435
African / African-American	0.004%	24,970
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.000763%	131,070

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser488=
Coding: c.1464C>T
MANE Select: NM_003062
dbSNP: rs774418931
Type: single nucleotide variant
Location: chr5:168762685 (GRCh38)
Structure: AlphaFold pLDDT 80.28
Residue 488: the lrrct 2 domain

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

Similar variants

SLIT3 p.Ser488Thr 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-ser488 (accessed [today's date]).

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