Is BPTF p.Asp185del (c.542ACG[4]) pathogenic?

BPTF p.Asp185del (c.542ACG[4]) is classified Benign/Likely benign in BPTF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Rare (popmax 0.969%, nfe); Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

What condition is associated with BPTF p.Asp185del (c.542ACG[4])?

BPTF p.Asp185del (c.542ACG[4]) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.Asp185del (c.542ACG[4]) in the general population?

BPTF p.Asp185del (c.542ACG[4]) is rare (popmax 0.969%, nfe) (gnomAD).

BPTF p.Asp185del

c.542ACG[4] · rs554343942 · VCV1806224

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.969%, nfe)

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.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.9	GERP -0.48, phastCons 1
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(GAC)n simple repeat, segmental duplication · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.969% European (non-Finnish) · 11,429/1,179,618 alleles

Filtering AF 0.954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.948%

Overall 0.868% 14,002/1,613,254 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.88%	35
European (non-Finnish)grpmax	0.969%	103
Remaining individualsnot grpmax-eligible	0.713%	140
Middle Eastern	0.189%	530
African / African-American	0.171%	586
Admixed American	0.155%	645
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,741
South Asian	0.0373%	2,678

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.Asp185del
Coding: c.542ACG[4]
dbSNP: rs554343942
Type: Microsatellite
Location: chr17:67826265 (GRCh38)

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

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-asp185del (accessed [today's date]).

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