Is BPTF p.Ser71fs (c.209dup) pathogenic?

BPTF p.Ser71fs (c.209dup) is classified Pathogenic in BPTF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-16). Ultra-rare (popmax 0.0202%, eas); Associated with BPTF-related disorder.

What condition is associated with BPTF p.Ser71fs (c.209dup)?

BPTF p.Ser71fs (c.209dup) is associated with BPTF-related disorder, neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.Ser71fs (c.209dup) in the general population?

BPTF p.Ser71fs (c.209dup) is ultra-rare (popmax 0.0202%, eas) (gnomAD).

BPTF p.Ser71fs

c.209dup · rs1259365489 · VCV1693493

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, eas)

Conditions

BPTF-related disorder

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 0.39	GERP 0.34, phastCons 0.85
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· 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 0.0202% East Asian · 2/9,878 alleles

Filtering AF 0.00354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.00128% 11/860,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0202%	4,939
Finnishnot grpmax-eligible	0.00852%	11,742
European (non-Finnish)	0.000945%	105,791

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.Ser71fs
Coding: c.209dup
MANE Select: NM_182641
dbSNP: rs1259365489
Type: Duplication
Location: chr17:67825926 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 71: the 'disordered' region

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

Disease context

BPTF-related disorder

Also linked: neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Similar variants

BPTF p.Ala1952fs Pathogenic ★ same condition
BPTF p.Ala2289fs Pathogenic ★ same condition
BPTF p.Arg2593fs Pathogenic ★ same condition
BPTF p.Asn2876Ter Likely pathogenic ★ same condition
BPTF p.Asp566fs Pathogenic ★ same condition
BPTF p.Gly2362fs Likely pathogenic ★ same condition
BPTF p.Thr1385fs Likely pathogenic ★ same condition
BPTF p.Thr2187fs Pathogenic ★ 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-ser71fs (accessed [today's date]).

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