Is B3GAT3 p.Pro331fs (c.992del) pathogenic?

B3GAT3 p.Pro331fs (c.992del) is classified Uncertain significance in B3GAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-16). Very rare (popmax 0.00834%, amr); Associated with Larsen-like syndrome, B3GAT3 type.

What condition is associated with B3GAT3 p.Pro331fs (c.992del)?

B3GAT3 p.Pro331fs (c.992del) is associated with Larsen-like syndrome, B3GAT3 type (ClinVar).

How common is B3GAT3 p.Pro331fs (c.992del) in the general population?

B3GAT3 p.Pro331fs (c.992del) is very rare (popmax 0.00834%, amr) (gnomAD).

B3GAT3 p.Pro331fs

c.992del · rs750535749 · VCV936655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

Larsen-like syndrome, B3GAT3 type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (5 of 5) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -2.6
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,982 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,613,616 alleles · very rare

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: B3GAT3
Protein: p.Pro331fs
Coding: c.992del
MANE Select: NM_012200
dbSNP: rs750535749
Type: Deletion
Location: chr11:62615717 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.67 · 3 PDB
Residue 331: the 'disordered' region

Full B3GAT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Larsen-like syndrome, B3GAT3 type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B3GAT3 c.909+263del Benign ★★ same condition
B3GAT3 p.Arg211fs Pathogenic ★ same condition
B3GAT3 p.Gln46fs Pathogenic ★ same condition
B3GAT3 p.Ile51fs Pathogenic ★ same condition
B3GAT3 p.Leu100fs Pathogenic ★ same condition
B3GAT3 p.Thr83fs Pathogenic ★ same condition
B3GAT3 p.Leu220_Gly222del Uncertain significance ★ same condition
B3GAT3 c.82+11del Likely 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/b3gat3-p-pro331fs (accessed [today's date]).

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