Is BPTF p.Ser86fs (c.255dup) pathogenic?

BPTF p.Ser86fs (c.255dup) is classified Conflicting classifications of pathogenicity in BPTF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-19). Ultra-rare (popmax 0.034%, eas).

How common is BPTF p.Ser86fs (c.255dup) in the general population?

BPTF p.Ser86fs (c.255dup) is ultra-rare (popmax 0.034%, eas) (gnomAD).

BPTF p.Ser86fs

c.255dup · rs1598050118 · VCV817433

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, eas)

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 1 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP 0.28, phastCons 1
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GCC)n simple repeat, segmental duplication · ambiguous alignment · 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 0.034% East Asian · 4/11,764 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00912%

Overall 0.0145% 127/875,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0634%	1,577
East Asiangrpmax	0.034%	2,941
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,923
Remaining individualsnot grpmax-eligible	0.0187%	5,340
South Asian	0.0136%	7,327
European (non-Finnish)	0.0117%	8,532
Admixed American	0.0117%	8,545
African / African-American	0.00176%	56,782

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: BPTF
Protein: p.Ser86fs
Coding: c.255dup
MANE Select: NM_182641
dbSNP: rs1598050118
Type: Duplication
Location: chr17:67825971 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 86: the 'disordered' region

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

Similar variants

BPTF p.Ser86Ile Uncertain significance ★ ⚠ same residue
BPTF p.Ser71fs Pathogenic ★★ same type
BPTF c.1864+712dup Likely pathogenic ★ same type
BPTF p.Ala1952fs Pathogenic ★ same type
BPTF p.Ala2289fs Pathogenic ★ same type
BPTF p.Arg2593fs Pathogenic ★ same type
BPTF p.Arg749fs Pathogenic ★ same type
BPTF p.Arg95fs Likely 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/bptf-p-ser86fs (accessed [today's date]).

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