Is ABAT p.Pro23His (c.68C>A) pathogenic?

ABAT p.Pro23His (c.68C>A) is classified Uncertain significance in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-18). AlphaMissense: likely benign (0.0844); Absent from gnomAD v4.1; Associated with GABA aminotransaminase deficiency.

What condition is associated with ABAT p.Pro23His (c.68C>A)?

ABAT p.Pro23His (c.68C>A) is associated with GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Pro23His (c.68C>A) in the general population?

ABAT p.Pro23His (c.68C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABAT p.Pro23His (c.68C>A)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

ABAT p.Pro23His

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

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

c.68C>A · rs369376388 · VCV1010607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,330)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GABA aminotransaminase deficiency

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -7.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP -0.62, phastCons 0.002
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	16.47	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

No allele count reported in gnomAD v4.1 (AN 1,602,330). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABAT
Protein: p.Pro23His
Coding: c.68C>A
MANE Select: NM_020686
dbSNP: rs369376388
Type: single nucleotide variant
Location: chr16:8735807 (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-pro23his (accessed [today's date]).

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