Is ABAT p.Arg250Leu (c.749G>T) pathogenic?

ABAT p.Arg250Leu (c.749G>T) is classified Uncertain significance in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely benign (0.1405); Ultra-rare (popmax 0.0658%, mid); Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Arg250Leu (c.749G>T)?

ABAT p.Arg250Leu (c.749G>T) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Arg250Leu (c.749G>T) in the general population?

ABAT p.Arg250Leu (c.749G>T) is ultra-rare (popmax 0.0658%, mid) (gnomAD).

What do computational predictors say about ABAT p.Arg250Leu (c.749G>T)?

AlphaMissense predicts likely benign (score 0.1405) — an in-silico prediction, not a clinical call.

ABAT p.Arg250Leu

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

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

c.749G>T · rs375002262 · VCV1419839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1405 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GABA aminotransaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.1405	likely benign
REVEL	0.597	indeterminate
SaProt	LLR -9.91	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	24.6	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 0.0658% Middle Eastern · 4/6,082 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.000434% 7/1,613,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0658%	1,521
European (non-Finnish)	0.000254%	393,343

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.Arg250Leu
Coding: c.749G>T
MANE Select: NM_020686
dbSNP: rs375002262
Type: single nucleotide variant
Location: chr16:8768906 (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.Arg250Gln Uncertain significance ★★ ⚠ same residue
ABAT p.Arg250Gly Uncertain significance ★ ⚠ same residue
ABAT p.Arg250= Likely benign ★ same residue
ABAT p.Arg250Trp 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-arg250leu (accessed [today's date]).

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