Is BAAT p.Ser333Gly (c.997A>G) pathogenic?

BAAT p.Ser333Gly (c.997A>G) is classified Conflicting classifications of pathogenicity in BAAT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-10-31). AlphaMissense: likely benign (0.1099); Rare (popmax 0.509%, afr); Associated with hypercholanemia, familial 1.

What condition is associated with BAAT p.Ser333Gly (c.997A>G)?

BAAT p.Ser333Gly (c.997A>G) is associated with hypercholanemia, familial 1 (ClinVar).

How common is BAAT p.Ser333Gly (c.997A>G) in the general population?

BAAT p.Ser333Gly (c.997A>G) is rare (popmax 0.509%, afr) (gnomAD).

How is Familial hypercholanemia inherited?

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

What do computational predictors say about BAAT p.Ser333Gly (c.997A>G)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

BAAT p.Ser333Gly

c.997A>G · rs139829321 · VCV289950

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.509%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypercholanemia, familial 1

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 8,973 bp · p 0.5 · regional, not allelic
Overall
CADD	18.59	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 0.509% African / African-American · 382/75,072 alleles

Filtering AF 0.467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.45%

Overall 0.0275% 444/1,614,220 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.509%	197
Middle Eastern	0.0495%	2,021
Admixed American	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0272%	3,677
European (non-Finnish)	0.00203%	49,168

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.Ser333Gly
Coding: c.997A>G
MANE Select: NM_001701
dbSNP: rs139829321
Type: single nucleotide variant
Location: chr9:101362688 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 333: 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

hypercholanemia, familial 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hypercholanemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

BAAT c.*1597C>A Uncertain significance ★★ same condition
BAAT p.Arg130Ser Uncertain significance ★★ ⚠ same condition
BAAT p.Asp42Glu Uncertain significance ★★ ⚠ same condition
BAAT p.Leu60= Uncertain significance ★★ same condition
BAAT p.Thr254Met Uncertain significance ★★ ⚠ same condition
BAAT c.*1029A>T Benign ★★ same condition
BAAT c.*1090A>G Benign ★★ same condition
BAAT c.*1458G>A Benign ★★ 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-ser333gly (accessed [today's date]).

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