Is B3GLCT p.Ser80fs (c.238dup) pathogenic?

B3GLCT p.Ser80fs (c.238dup) is classified Likely pathogenic in B3GLCT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-04). Very rare (popmax 0.00667%, afr).

How common is B3GLCT p.Ser80fs (c.238dup) in the general population?

B3GLCT p.Ser80fs (c.238dup) is very rare (popmax 0.00667%, afr) (gnomAD).

B3GLCT p.Ser80fs

c.238dup · rs772504695 · VCV817468

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,914 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00248% 40/1,612,462 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,983
Finnishnot grpmax-eligible	0.00625%	15,999
Remaining individualsnot grpmax-eligible	0.0032%	31,225
East Asian	0.00223%	44,868
South Asian	0.0022%	45,524
European (non-Finnish)	0.00212%	47,146
Admixed American	0.00167%	59,986

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: B3GLCT
Protein: p.Ser80fs
Coding: c.238dup
MANE Select: NM_194318
dbSNP: rs772504695
Type: Duplication
Location: chr13:31229254 (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

Similar variants

B3GLCT p.Ser80Asn Uncertain significance ★ ⚠ same residue
B3GLCT c.161-8dup Benign ★★ same type
B3GLCT c.781-34_781-31dup Benign ★★ same type
B3GLCT c.781-3dup Uncertain significance ★ same type
B3GLCT p.Asp452fs 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-ser80fs (accessed [today's date]).

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