Is BAAT p.Val304Ala (c.911T>C) pathogenic?

BAAT p.Val304Ala (c.911T>C) is classified Benign in BAAT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0597); Low-frequency (popmax 4.59%, mid); Associated with hypercholanemia, familial 1.

What condition is associated with BAAT p.Val304Ala (c.911T>C)?

BAAT p.Val304Ala (c.911T>C) is associated with hypercholanemia, familial 1 (ClinVar).

How common is BAAT p.Val304Ala (c.911T>C) in the general population?

BAAT p.Val304Ala (c.911T>C) is low-frequency (popmax 4.59%, mid) (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.Val304Ala (c.911T>C)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

BAAT p.Val304Ala

c.911T>C · rs61755096 · VCV258174

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.59%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypercholanemia, familial 1

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.31	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 -6.6	GERP -3.1
Regional constraint	o/e 0.97	unconstrained · MANE · 8,973 bp · p 0.5 · regional, not allelic
Overall
CADD	0.001	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 4.59% Middle Eastern · 278/6,062 alleles

Filtering AF 4.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.12%

Overall 2.69% 43,454/1,614,172 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	6.94%	14
Middle Easterngrpmax	4.59%	22
South Asian	4.28%	23
European (non-Finnish)	2.86%	35
Remaining individualsnot grpmax-eligible	2.82%	35
Admixed American	1.98%	50
Amishnot grpmax-eligible	0.44%	228
African / African-American	0.426%	235
Finnishnot grpmax-eligible	0.275%	364
East Asian	0.00891%	11,219

Ashkenazi Jewish 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.Val304Ala
Coding: c.911T>C
MANE Select: NM_001701
dbSNP: rs61755096
Type: single nucleotide variant
Location: chr9:101362774 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 304: 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-val304ala (accessed [today's date]).

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