Is BPTF p.Arg95fs (c.282dup) pathogenic?

BPTF p.Arg95fs (c.282dup) is classified Likely pathogenic in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). Rare (popmax 0.129%, eas).

How common is BPTF p.Arg95fs (c.282dup) in the general population?

BPTF p.Arg95fs (c.282dup) is rare (popmax 0.129%, eas) (gnomAD).

BPTF p.Arg95fs

c.282dup · rs1438959480 · VCV3252820

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.129%, 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 2.7	GERP 0.33, phastCons 1
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(CGG)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 0.129% East Asian · 25/19,440 alleles

Filtering AF 0.0893% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.0519% 345/664,116 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.129%	778
Finnishnot grpmax-eligible	0.0987%	1,014
Remaining individualsnot grpmax-eligible	0.0826%	1,211
European (non-Finnish)	0.0511%	1,958
South Asian	0.0449%	2,226
Ashkenazi Jewishnot grpmax-eligible	0.0286%	3,494
Admixed American	0.0219%	4,562
African / African-American	0.0178%	5,607

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.Arg95fs
Coding: c.282dup
MANE Select: NM_182641
dbSNP: rs1438959480
Type: Duplication
Location: chr17:67825998 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 95: the 'disordered' region

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

Similar variants

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.Asn2876Ter Likely pathogenic ★ same type
BPTF p.Asp566fs 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-arg95fs (accessed [today's date]).

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