Is BAX p.Glu41fs (c.121dup) pathogenic?

BAX p.Glu41fs (c.121dup) is classified Uncertain significance in BAX (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-18). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with BAX p.Glu41fs (c.121dup)?

BAX p.Glu41fs (c.121dup) is associated with Inborn genetic diseases, colon carcinoma (ClinVar).

How common is BAX p.Glu41fs (c.121dup) in the general population?

BAX p.Glu41fs (c.121dup) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

BAX p.Glu41fs

c.121dup · rs398122840 · VCV9511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

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 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Overall
CADD	33.0	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 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00199%

Overall 0.00566% 91/1,609,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.076%	1,316
Middle Easterngrpmax	0.0165%	6,058
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,430
South Asian	0.00331%	30,242
European (non-Finnish)	0.00306%	32,720
East Asian	0.00223%	44,756
African / African-American	0.00135%	74,342

Finnish 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: BAX
Protein: p.Glu41fs
Coding: c.121dup
MANE Select: NM_138761
dbSNP: rs398122840
Type: Duplication
Location: chr19:48955713 (GRCh38)
Gene constraint: LOEUF 1.245 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.71 · 37 PDB
Residue 41: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colon carcinoma

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/bax-p-glu41fs (accessed [today's date]).

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