Is BPTF p.2676APP[4] (c.8035GCCCCTCCA[3]) pathogenic?

BPTF p.2676APP[4] (c.8035GCCCCTCCA[3]) is classified Benign in BPTF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 61.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

What condition is associated with BPTF p.2676APP[4] (c.8035GCCCCTCCA[3])?

BPTF p.2676APP[4] (c.8035GCCCCTCCA[3]) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.2676APP[4] (c.8035GCCCCTCCA[3]) in the general population?

BPTF p.2676APP[4] (c.8035GCCCCTCCA[3]) is common (popmax 61.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

BPTF p.2676APP[4]

c.8035GCCCCTCCA[3] · rs60308484 · VCV1175512

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 61.1%, eas) — too common for a highly-penetrant pathogenic allele

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 assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.7	GERP -1.8
Overall
CADD	4.587	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	CCAGCCCCT simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.1% East Asian · 23,120/37,810 alleles

Filtering AF 60.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.2%

Overall 15.6% 238,585/1,527,250 alleles · common exomes 212,052/1,382,572 · genomes 26,533/144,678 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	61.1%	2
Finnishnot grpmax-eligible	20.1%	5
Admixed American	19%	5
South Asian	17.3%	6
Remaining individualsnot grpmax-eligible	16.9%	6
Middle Eastern	15.3%	7
African / African-American	14.7%	7
European (non-Finnish)	13.7%	7
Ashkenazi Jewishnot grpmax-eligible	10.2%	10
Amishnot grpmax-eligible	5.16%	19

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.2676APP[4]
Coding: c.8035GCCCCTCCA[3]
MANE Select: NM_182641
dbSNP: rs60308484
Type: Microsatellite
Location: chr17:67959642 (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.Asp184_Asp185dup Uncertain significance ★★ same condition
BPTF p.Val1613fs Pathogenic ★ same condition
BPTF p.Arg1859fs Pathogenic same condition
BPTF p.Ile1883del Uncertain significance same condition
BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ same condition
BPTF p.Arg2858Ter Pathogenic ★★ same condition
BPTF p.Ser71fs Pathogenic ★★ same condition
BPTF p.Arg2058Cys Uncertain significance ★★ 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-2676app-4 (accessed [today's date]).

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