Is B3GLCT p.Asp452fs (c.1354dup) pathogenic?

B3GLCT p.Asp452fs (c.1354dup) is classified Uncertain significance in B3GLCT (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with Marfanoid habitus and intellectual disability.

What condition is associated with B3GLCT p.Asp452fs (c.1354dup)?

B3GLCT p.Asp452fs (c.1354dup) is associated with Marfanoid habitus and intellectual disability (ClinVar).

How common is B3GLCT p.Asp452fs (c.1354dup) in the general population?

B3GLCT p.Asp452fs (c.1354dup) is absent from gnomAD (gnomAD).

B3GLCT p.Asp452fs

c.1354dup · rs1593326694 · VCV689667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Marfanoid habitus and intellectual disability

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 (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP -0.24, phastCons 0.92

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: B3GLCT
Protein: p.Asp452fs
Coding: c.1354dup
MANE Select: NM_194318
dbSNP: rs1593326694
Type: Duplication
Location: chr13:31329523 (GRCh38)
Gene constraint: LOEUF 1.109 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB

Full B3GLCT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Marfanoid habitus and intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

B3GLCT c.161-8dup Benign ★★ same type
B3GLCT c.781-34_781-31dup Benign ★★ same type
B3GLCT p.Ser80fs Likely pathogenic ★ same type
B3GLCT c.781-3dup Uncertain significance ★ same type
B3GLCT c.1184+302dup Benign ★ same type
B3GLCT c.347+199dup Likely benign ★ same type
B3GLCT p.Leu77fs Pathogenic 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/b3glct-p-asp452fs (accessed [today's date]).

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