Is BPTF p.Asp566fs (c.1691dup) pathogenic?

BPTF p.Asp566fs (c.1691dup) is classified Pathogenic in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-11). Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

What condition is associated with BPTF p.Asp566fs (c.1691dup)?

BPTF p.Asp566fs (c.1691dup) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

BPTF p.Asp566fs

c.1691dup · VCV4847311

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

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 4 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP -0.58, phastCons 1

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

Variant & gene context

Gene: BPTF
Protein: p.Asp566fs
Coding: c.1691dup
MANE Select: NM_182641
Type: Duplication
Location: chr17:67874842 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Ser71fs Pathogenic ★★ same condition
BPTF p.Asp566His Uncertain significance ★★ ⚠ same residue
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.Gly2362fs Likely pathogenic ★ same condition
BPTF p.Thr1385fs Likely 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-asp566fs (accessed [today's date]).

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