Is BAAT p.Arg130Ser (c.390G>T) pathogenic?

BAAT p.Arg130Ser (c.390G>T) is classified Uncertain significance in BAAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.9464); Very rare (popmax 0.00356%, nfe); Associated with hypercholanemia, familial 1.

What condition is associated with BAAT p.Arg130Ser (c.390G>T)?

BAAT p.Arg130Ser (c.390G>T) is associated with hypercholanemia, familial 1 (ClinVar).

How common is BAAT p.Arg130Ser (c.390G>T) in the general population?

BAAT p.Arg130Ser (c.390G>T) is very rare (popmax 0.00356%, nfe) (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.Arg130Ser (c.390G>T)?

AlphaMissense predicts likely pathogenic (score 0.9464) — an in-silico prediction, not a clinical call.

BAAT p.Arg130Ser

c.390G>T · rs551090726 · VCV912408

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9464 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypercholanemia, familial 1

Computational evidence

Protein change
AlphaMissense	0.9464	likely pathogenic · top 1% in BAAT
REVEL	0.72	pathogenic-leaning
SaProt	LLR -12.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -2.7, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 8,973 bp · p 0.5 · regional, not allelic
Overall
CADD	19.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00356% European (non-Finnish) · 42/1,180,024 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00279% 45/1,614,146 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,096
East Asian	0.00223%	44,868
Finnishnot grpmax-eligible	0.00156%	64,034
South Asian	0.0011%	91,084

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.Arg130Ser
Coding: c.390G>T
MANE Select: NM_001701
dbSNP: rs551090726
Type: single nucleotide variant
Location: chr9:101371015 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 130: 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.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
BAAT c.*1475G>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-arg130ser (accessed [today's date]).

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