Is BAAT p.Leu60= (c.178C>T) pathogenic?

BAAT p.Leu60= (c.178C>T) is classified Uncertain significance in BAAT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-13). Ultra-rare (popmax 0.0131%, nfe); Associated with hypercholanemia, familial 1.

What condition is associated with BAAT p.Leu60= (c.178C>T)?

BAAT p.Leu60= (c.178C>T) is associated with hypercholanemia, familial 1 (ClinVar).

How common is BAAT p.Leu60= (c.178C>T) in the general population?

BAAT p.Leu60= (c.178C>T) is ultra-rare (popmax 0.0131%, nfe) (gnomAD).

How is Familial hypercholanemia inherited?

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

BAAT p.Leu60=

c.178C>T · rs374248798 · VCV364282

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, nfe)

Conditions

hypercholanemia, familial 1

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
Constraint at this position
Conservation	phyloP 1.5	GERP -0.32, phastCons 0.69
Overall
CADD	5.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0131% European (non-Finnish) · 154/1,179,458 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00992% 160/1,613,312 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0131%	7,659
Admixed American	0.005%	19,981
Remaining individualsnot grpmax-eligible	0.0048%	20,817

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.Leu60=
Coding: c.178C>T
MANE Select: NM_001701
dbSNP: rs374248798
Type: single nucleotide variant
Location: chr9:101371227 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 60: 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.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-leu60 (accessed [today's date]).

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