Is BAAT p.Met76Val (c.226A>G) pathogenic?

BAAT p.Met76Val (c.226A>G) is classified Pathogenic in BAAT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2003-05-01). AlphaMissense: likely benign (0.2783); Very rare (popmax 0.00223%, eas); Associated with bile acid conjugation defect 1.

What condition is associated with BAAT p.Met76Val (c.226A>G)?

BAAT p.Met76Val (c.226A>G) is associated with bile acid conjugation defect 1 (ClinVar).

How common is BAAT p.Met76Val (c.226A>G) in the general population?

BAAT p.Met76Val (c.226A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BAAT p.Met76Val (c.226A>G)?

AlphaMissense predicts likely benign (score 0.2783) — an in-silico prediction, not a clinical call.

BAAT p.Met76Val

c.226A>G · rs28937579 · VCV6720

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2783 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

bile acid conjugation defect 1

Computational evidence

Protein change
AlphaMissense	0.2783	likely benign ⚠ discordant with ClinVar
REVEL	0.71	pathogenic-leaning
SaProt	LLR -12.42	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.54, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,973 bp · p 0.5 · regional, not allelic
Overall
CADD	24.4	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00242% 39/1,614,160 alleles · very rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.63%	38
Remaining individualsnot grpmax-eligible	0.0032%	31,255
East Asiangrpmax	0.00223%	44,882
African / African-American	0.00133%	75,048
European (non-Finnish)	0.000932%	107,274

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met76Val
Coding: c.226A>G
MANE Select: NM_001701
dbSNP: rs28937579
Type: single nucleotide variant
Location: chr9:101371179 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 76: a UniProt-annotated variant site (in fhca3; contrary to wild-type, undetectable expression in hepatocytes); a UniProt-annotated variant site (in fhca3)

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.Met76Thr Uncertain significance ★★ ⚠ same residue
BAAT p.Leu284Ter Uncertain significance ★★ same condition
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

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-met76val (accessed [today's date]).

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