Is SLC6A9 p.Pro382= (c.1146G>A) pathogenic?

SLC6A9 p.Pro382= (c.1146G>A) is classified Benign in SLC6A9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.42%, nfe); Associated with atypical glycine encephalopathy.

What condition is associated with SLC6A9 p.Pro382= (c.1146G>A)?

SLC6A9 p.Pro382= (c.1146G>A) is associated with atypical glycine encephalopathy (ClinVar).

How common is SLC6A9 p.Pro382= (c.1146G>A) in the general population?

SLC6A9 p.Pro382= (c.1146G>A) is low-frequency (popmax 1.42%, nfe) (gnomAD).

How is Glycine encephalopathy inherited?

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

SLC6A9 p.Pro382=

c.1146G>A · rs76354303 · VCV774154

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, nfe)

Conditions

atypical glycine encephalopathy

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 -20	GERP -3.9
Overall
CADD	0.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% European (non-Finnish) · 16,789/1,179,902 alleles

Filtering AF 1.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 1.19% 19,242/1,613,966 alleles · low-frequency exomes 17,887/1,461,712 · genomes 1,355/152,254 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2%	50
European (non-Finnish)grpmax	1.42%	70
Middle Eastern	1.22%	82
Remaining individualsnot grpmax-eligible	1.19%	84
Admixed American	0.862%	116
African / African-American	0.255%	393
Finnishnot grpmax-eligible	0.223%	448
South Asian	0.213%	469
East Asian	0.00223%	44,886

Ashkenazi Jewish 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: SLC6A9
Protein: p.Pro382=
Coding: c.1146G>A
MANE Select: NM_001024845
dbSNP: rs76354303
Type: single nucleotide variant
Location: chr1:44001444 (GRCh38)
Gene constraint: LOEUF 0.544 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 81.95 · 9 PDB
Residue 382: an α-helix

Full SLC6A9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atypical glycine encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycine encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

SLC6A9 p.Pro382Ser Uncertain significance ★ same residue
SLC6A9 c.1536+1G>A Likely pathogenic ★★ same condition
SLC6A9 p.Gln278Ter Pathogenic/Likely pathogenic ★★ same condition
SLC6A9 c.31-6226C>T Uncertain significance ★★ ⚠ same condition
SLC6A9 c.31-731A>C Uncertain significance ★★ ⚠ same condition
SLC6A9 c.31-825G>A Uncertain significance ★★ ⚠ same condition
SLC6A9 p.Ala538Val Uncertain significance ★★ ⚠ same condition
SLC6A9 p.Arg260His Uncertain significance ★★ ⚠ 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/slc6a9-p-pro382 (accessed [today's date]).

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