Is ABAT p.Arg250Trp (c.748C>T) pathogenic?

ABAT p.Arg250Trp (c.748C>T) is classified Likely benign in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). AlphaMissense: likely benign (0.133); Rare (popmax 0.234%, eas); Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Arg250Trp (c.748C>T)?

ABAT p.Arg250Trp (c.748C>T) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Arg250Trp (c.748C>T) in the general population?

ABAT p.Arg250Trp (c.748C>T) is rare (popmax 0.234%, eas) (gnomAD).

What do computational predictors say about ABAT p.Arg250Trp (c.748C>T)?

AlphaMissense predicts likely benign (score 0.133) — an in-silico prediction, not a clinical call.

ABAT p.Arg250Trp

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

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

c.748C>T · rs201397255 · VCV460329

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.133 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.234%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GABA aminotransaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.133	likely benign
REVEL	0.474	indeterminate
SaProt	LLR -12.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.074	GERP -1.3, phastCons 0.002
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.234% East Asian · 105/44,872 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.00991% 160/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.234%	427
South Asian	0.0176%	5,692
African / African-American	0.012%	8,338
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.0022%	45,386

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.Arg250Trp
Coding: c.748C>T
MANE Select: NM_020686
dbSNP: rs201397255
Type: single nucleotide variant
Location: chr16:8768905 (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.Arg250Leu Uncertain significance ★ ⚠ same residue
ABAT p.Arg250= 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-arg250trp (accessed [today's date]).

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