Is ABAT p.Arg19His (c.56G>A) pathogenic?

ABAT p.Arg19His (c.56G>A) is classified Uncertain significance in ABAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-18). AlphaMissense: likely benign (0.0787); Ultra-rare (popmax 0.0348%, sas); Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Arg19His (c.56G>A)?

ABAT p.Arg19His (c.56G>A) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Arg19His (c.56G>A) in the general population?

ABAT p.Arg19His (c.56G>A) is ultra-rare (popmax 0.0348%, sas) (gnomAD).

What do computational predictors say about ABAT p.Arg19His (c.56G>A)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

ABAT p.Arg19His

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

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

c.56G>A · rs780368959 · VCV529790

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0348%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GABA aminotransaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -4.9
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	5.435	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 0.0348% South Asian · 31/89,034 alleles

Filtering AF 0.0252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00399% 64/1,603,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0348%	2,872
Middle Eastern	0.0165%	6,076
African / African-American	0.00534%	18,712
Remaining individualsnot grpmax-eligible	0.00483%	20,717
East Asian	0.00447%	22,375
Finnishnot grpmax-eligible	0.0032%	31,286
Admixed American	0.0017%	58,702
European (non-Finnish)	0.0017%	58,774

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.Arg19His
Coding: c.56G>A
MANE Select: NM_020686
dbSNP: rs780368959
Type: single nucleotide variant
Location: chr16:8735795 (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.Arg19Ser Uncertain significance ★★ ⚠ same residue
ABAT p.Arg19Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ABAT p.Arg19Leu Uncertain significance ★ ⚠ same residue
ABAT p.Arg19= Likely benign ★ 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

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-arg19his (accessed [today's date]).

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