Is SLC6A1 p.Ser331= (c.993C>T) pathogenic?

SLC6A1 p.Ser331= (c.993C>T) is classified Benign in SLC6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Very rare (popmax 0.00534%, afr); Associated with epilepsy with myoclonic atonic seizures.

What condition is associated with SLC6A1 p.Ser331= (c.993C>T)?

SLC6A1 p.Ser331= (c.993C>T) is associated with epilepsy with myoclonic atonic seizures (ClinVar).

How common is SLC6A1 p.Ser331= (c.993C>T) in the general population?

SLC6A1 p.Ser331= (c.993C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Epilepsy with myoclonic-atonic seizures inherited?

Typically Unknown (Orphanet). A genetic counselor can assess individual risk for a family.

SLC6A1 p.Ser331=

c.993C>T · rs376992822 · VCV940556

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

epilepsy with myoclonic atonic seizures

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP -0.53, phastCons 1
Overall
CADD	13.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,910 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,613,922 alleles · very rare exomes 1/1,461,796 · genomes 3/152,126 · 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: SLC6A1
Protein: p.Ser331=
Coding: c.993C>T
MANE Select: NM_003042
dbSNP: rs376992822
Type: single nucleotide variant
Location: chr3:11026274 (GRCh38)
Gene constraint: LOEUF 0.153 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.57 · 5 PDB
Residue 331: an α-helix

Full SLC6A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy with myoclonic atonic seizures — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Epilepsy with myoclonic-atonic seizures (Orphanet):

Inheritance: Unknown
Onset: Childhood

Similar variants

SLC6A1 p.Ser331Gly Uncertain significance ★ same residue
SLC6A1 c.1192-2A>G Pathogenic/Likely pathogenic ★★ same condition
SLC6A1 c.1528-1G>A Pathogenic ★★ same condition
SLC6A1 p.Ala288Val Pathogenic/Likely pathogenic ★★ same condition
SLC6A1 p.Ala357Val Pathogenic ★★ ⚠ same condition
SLC6A1 p.Arg44Trp Pathogenic/Likely pathogenic ★★ same condition
SLC6A1 p.Arg479Ter Pathogenic ★★ same condition
SLC6A1 p.Gln106Arg 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/slc6a1-p-ser331 (accessed [today's date]).

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