Is ABAT p.Ser149= (c.447G>T) pathogenic?

ABAT p.Ser149= (c.447G>T) is classified Conflicting classifications of pathogenicity in ABAT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-08). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with ABAT p.Ser149= (c.447G>T)?

ABAT p.Ser149= (c.447G>T) is associated with Inborn genetic diseases, GABA aminotransaminase deficiency (ClinVar).

How common is ABAT p.Ser149= (c.447G>T) in the general population?

ABAT p.Ser149= (c.447G>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ABAT p.Ser149=

c.447G>T · rs376531387 · VCV1503220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -2.5	GERP -3.7
Overall
CADD	14.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00291% 47/1,612,756 alleles · ultra-rare exomes 40/1,460,672 · genomes 7/152,084 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0144%	6,941
Finnishnot grpmax-eligible	0.0127%	7,889
European (non-Finnish)	0.00237%	42,135
South Asian	0.0011%	91,064

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.Ser149=
Coding: c.447G>T
MANE Select: NM_020686
dbSNP: rs376531387
Type: single nucleotide variant
Location: chr16:8764149 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GABA aminotransaminase deficiency

Similar variants

ABAT p.Ser149Leu Uncertain significance ★★ ⚠ same residue
ABAT p.Ser149Trp Uncertain significance ★ ⚠ 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
ABAT p.Tyr376Ter Pathogenic/Likely pathogenic ★★ same condition
ABAT c.1381+6G>T 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-ser149 (accessed [today's date]).

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