Is SLC6A1 p.Pro85= (c.255C>T) pathogenic?

SLC6A1 p.Pro85= (c.255C>T) is classified Likely benign in SLC6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). Absent from gnomAD v4.1; Associated with epilepsy with myoclonic atonic seizures.

What condition is associated with SLC6A1 p.Pro85= (c.255C>T)?

SLC6A1 p.Pro85= (c.255C>T) is associated with epilepsy with myoclonic atonic seizures (ClinVar).

How common is SLC6A1 p.Pro85= (c.255C>T) in the general population?

SLC6A1 p.Pro85= (c.255C>T) is absent from gnomAD v4.1 (gnomAD).

How is Epilepsy with myoclonic-atonic seizures inherited?

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

SLC6A1 p.Pro85=

c.255C>T · VCV3731560

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -2.8, phastCons 0.011
Overall
CADD	9.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC6A1
Protein: p.Pro85=
Coding: c.255C>T
MANE Select: NM_003042
Type: single nucleotide variant
Location: chr3:11017859 (GRCh38)
Gene constraint: LOEUF 0.153 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.57 · 5 PDB
Residue 85: 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 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
SLC6A1 p.Gln534Ter 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-pro85 (accessed [today's date]).

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