Is BAAT p.Arg146His (c.437G>A) pathogenic?

BAAT p.Arg146His (c.437G>A) is classified Uncertain significance in BAAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). AlphaMissense: likely benign (0.1086); Ultra-rare (popmax 0.0242%, sas).

How common is BAAT p.Arg146His (c.437G>A) in the general population?

BAAT p.Arg146His (c.437G>A) is ultra-rare (popmax 0.0242%, sas) (gnomAD).

What do computational predictors say about BAAT p.Arg146His (c.437G>A)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

BAAT p.Arg146His

c.437G>A · VCV3713724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -9.25	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 -1	GERP -0.16
Regional constraint	o/e 0.97	unconstrained · MANE · 8,973 bp · p 0.5 · regional, not allelic
Overall
CADD	17.16	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0242% South Asian · 22/91,086 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00458% 74/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,140
European (non-Finnish)	0.00415%	24,082
Remaining individualsnot grpmax-eligible	0.0032%	31,242
East Asian	0.00223%	44,868

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.Arg146His
Coding: c.437G>A
MANE Select: NM_001701
Type: single nucleotide variant
Location: chr9:101370968 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.31
Residue 146: 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

Similar variants

BAAT p.Arg146Cys Uncertain significance ★ ⚠ same residue
BAAT c.*1597C>A Uncertain significance ★★ same type
BAAT p.Ala337Thr Uncertain significance ★★ ⚠ same type
BAAT p.Arg130Ser Uncertain significance ★★ ⚠ same type
BAAT p.Asp42Glu Uncertain significance ★★ ⚠ same type
BAAT p.Glu54Lys Uncertain significance ★★ ⚠ same type
BAAT p.Gly41Arg Uncertain significance ★★ ⚠ same type
BAAT p.His74Tyr Uncertain significance ★★ ⚠ same type

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-arg146his (accessed [today's date]).

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