Is ABAT p.Ala111Asp (c.332C>A) pathogenic?

ABAT p.Ala111Asp (c.332C>A) is classified Uncertain significance in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely benign (0.1824); Very rare (popmax 0.00329%, sas); Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Ala111Asp (c.332C>A)?

ABAT p.Ala111Asp (c.332C>A) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Ala111Asp (c.332C>A) in the general population?

ABAT p.Ala111Asp (c.332C>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about ABAT p.Ala111Asp (c.332C>A)?

AlphaMissense predicts likely benign (score 0.1824) — an in-silico prediction, not a clinical call.

ABAT p.Ala111Asp

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

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

c.332C>A · rs771274821 · VCV941758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GABA aminotransaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.1824	likely benign
REVEL	0.573	indeterminate
SaProt	LLR -3.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,072 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000274% 4/1,461,836 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,357
European (non-Finnish)	8.47e-05%	1,179,990

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.Ala111Asp
Coding: c.332C>A
MANE Select: NM_020686
dbSNP: rs771274821
Type: single nucleotide variant
Location: chr16:8757772 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.91

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.Ala111Thr 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-ala111asp (accessed [today's date]).

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