Is ABAT p.Ile396Val (c.1186A>G) pathogenic?

ABAT p.Ile396Val (c.1186A>G) is classified Conflicting classifications of pathogenicity in ABAT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0804); Rare (popmax 0.394%, afr); Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Ile396Val (c.1186A>G)?

ABAT p.Ile396Val (c.1186A>G) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Ile396Val (c.1186A>G) in the general population?

ABAT p.Ile396Val (c.1186A>G) is rare (popmax 0.394%, afr) (gnomAD).

What do computational predictors say about ABAT p.Ile396Val (c.1186A>G)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

ABAT p.Ile396Val

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

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

c.1186A>G · rs150914629 · VCV585340

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.394%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GABA aminotransaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -5.74	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 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	18.87	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 0.394% African / African-American · 296/75,050 alleles

Filtering AF 0.357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.343%

Overall 0.0204% 329/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.394%	254
Remaining individualsnot grpmax-eligible	0.0208%	4,809
Admixed American	0.0183%	5,457
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.000678%	147,503

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.Ile396Val
Coding: c.1186A>G
MANE Select: NM_020686
dbSNP: rs150914629
Type: single nucleotide variant
Location: chr16:8776407 (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 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
ABAT p.Ala226Val 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-ile396val (accessed [today's date]).

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