Is SLC6A1 p.Val511= (c.1533G>A) pathogenic?

SLC6A1 p.Val511= (c.1533G>A) is classified Likely benign in SLC6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-09). Very rare (popmax 0.00167%, amr); Associated with epilepsy with myoclonic atonic seizures.

What condition is associated with SLC6A1 p.Val511= (c.1533G>A)?

SLC6A1 p.Val511= (c.1533G>A) is associated with epilepsy with myoclonic atonic seizures (ClinVar).

How common is SLC6A1 p.Val511= (c.1533G>A) in the general population?

SLC6A1 p.Val511= (c.1533G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Epilepsy with myoclonic-atonic seizures inherited?

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

SLC6A1 p.Val511=

c.1533G>A · rs1276757037 · VCV1650423

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.6	GERP -0.53, phastCons 1
Overall
CADD	10.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,958 alleles

Overall 6.21e-05% 1/1,610,338 alleles · very rare exomes 1/1,458,236 · genomes 0/152,102 · 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.Val511=
Coding: c.1533G>A
MANE Select: NM_003042
dbSNP: rs1276757037
Type: single nucleotide variant
Location: chr3:11034536 (GRCh38)
Gene constraint: LOEUF 0.153 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.57 · 5 PDB
Residue 511: a UniProt-annotated variant site (found in a patient with generalized epilepsy; uncertain significance; complete loss of gaba transporter activity); 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.Val511Leu Likely pathogenic ★★ ⚠ same residue
SLC6A1 p.Val511Met Pathogenic/Likely pathogenic ★★ ⚠ 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

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-val511 (accessed [today's date]).

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