Is ABAT p.Cys321= (c.963C>T) pathogenic?

ABAT p.Cys321= (c.963C>T) is classified Likely benign in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). Ultra-rare (popmax 0.0187%, afr); Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Cys321= (c.963C>T)?

ABAT p.Cys321= (c.963C>T) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Cys321= (c.963C>T) in the general population?

ABAT p.Cys321= (c.963C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

ABAT p.Cys321=

Q: How is Gamma-aminobutyric acid transaminase deficiency inherited?

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

c.963C>T · rs375537349 · VCV1130478

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

GABA aminotransaminase deficiency

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 -0.11	GERP -3.6, phastCons 0.82
Overall
CADD	9.284	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/75,052 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.00211% 34/1,614,030 alleles · ultra-rare exomes 27/1,461,744 · genomes 7/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,361
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.005%	20,004
East Asian	0.00446%	22,438
South Asian	0.0011%	91,076
European (non-Finnish)	0.000763%	131,113

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: ABAT
Protein: p.Cys321=
Coding: c.963C>T
MANE Select: NM_020686
dbSNP: rs375537349
Type: single nucleotide variant
Location: chr16:8774898 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.91
Residue 321: a disulfide bond

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

Disease context

GABA aminotransaminase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gamma-aminobutyric acid transaminase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ABAT p.Cys321Arg Uncertain significance ★★ ⚠ same residue
ABAT c.168+1G>A Pathogenic ★★ same condition
ABAT p.Arg92Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABAT p.Gln8Ter Pathogenic/Likely pathogenic ★★ same condition
ABAT p.Leu211Phe Pathogenic/Likely pathogenic ★★ same condition
ABAT p.Tyr376Ter Pathogenic/Likely pathogenic ★★ same condition
ABAT c.1381+6G>T Uncertain significance ★★ same condition
ABAT p.Ala162Thr 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/abat-p-cys321 (accessed [today's date]).

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