Is BPTF p.Glu867fs (c.2598dup) pathogenic?

BPTF p.Glu867fs (c.2598dup) is classified Conflicting classifications of pathogenicity in BPTF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-03). Ultra-rare (popmax 0.0525%, amr); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Glu867fs (c.2598dup)?

BPTF p.Glu867fs (c.2598dup) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Glu867fs (c.2598dup) in the general population?

BPTF p.Glu867fs (c.2598dup) is ultra-rare (popmax 0.0525%, amr) (gnomAD).

BPTF p.Glu867fs

c.2598dup · rs753044214 · VCV520550

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0525%, amr)

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 in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 8 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.3	GERP -4.6
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	A-rich low complexity · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0525% Admixed American · 27/51,412 alleles

Filtering AF 0.037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0318%

Overall 0.0159% 245/1,540,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0525%	1,904
South Asian	0.0393%	2,546
Remaining individualsnot grpmax-eligible	0.0303%	3,296
East Asian	0.0188%	5,310
African / African-American	0.0142%	7,029
European (non-Finnish)	0.0126%	7,965
Ashkenazi Jewishnot grpmax-eligible	0.0106%	9,396
Finnishnot grpmax-eligible	0.00655%	15,277

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: BPTF
Protein: p.Glu867fs
Coding: c.2598dup
MANE Select: NM_182641
dbSNP: rs753044214
Type: Duplication
Location: chr17:67903834 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 867: the 'interaction with maz' region

Full BPTF 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

Similar variants

BPTF p.Gln2348fs Pathogenic ★ same condition
BPTF p.Thr483fs Pathogenic ★ same condition
BPTF p.Thr783fs Pathogenic ★★ same condition
BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala2819Phe Uncertain significance ★★ same condition
BPTF p.Arg1078Gln Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ 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/bptf-p-glu867fs (accessed [today's date]).

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