Is BAAT p.Leu284Ter (c.851T>G) pathogenic?

BAAT p.Leu284Ter (c.851T>G) is classified Uncertain significance in BAAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-23). Ultra-rare (popmax 0.0133%, amr); Associated with bile acid conjugation defect 1.

What condition is associated with BAAT p.Leu284Ter (c.851T>G)?

BAAT p.Leu284Ter (c.851T>G) is associated with bile acid conjugation defect 1 (ClinVar).

How common is BAAT p.Leu284Ter (c.851T>G) in the general population?

BAAT p.Leu284Ter (c.851T>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

BAAT p.Leu284Ter

c.851T>G · rs1419255104 · VCV500560

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

bile acid conjugation defect 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -3.1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,996 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000496% 8/1,614,046 alleles · ultra-rare

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: BAAT
Protein: p.Leu284Ter
Coding: c.851T>G
MANE Select: NM_001701
dbSNP: rs1419255104
Type: single nucleotide variant
Location: chr9:101362834 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 284: a UniProt-annotated variant site (in fhca3; contrary to wild-type, undetectable expression in hepatocytes)

Full BAAT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

bile acid conjugation defect 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAAT p.Met1Lys Uncertain significance ★★ same condition
BAAT p.Thr254Met Uncertain significance ★★ ⚠ same condition
BAAT c.*46G>A Benign ★★ same condition
BAAT p.Arg20Gln Benign ★★ same condition
BAAT p.Ser233Pro Uncertain significance ★ ⚠ same condition
BAAT p.Val229Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
BAAT p.Arg20Ter Pathogenic same condition
BAAT p.Asp69Val 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/baat-p-leu284ter (accessed [today's date]).

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