Is BPTF p.Pro2787= (c.8361A>T) pathogenic?

BPTF p.Pro2787= (c.8361A>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-08). Very rare (popmax 0.00223%, eas); Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

How common is BPTF p.Pro2787= (c.8361A>T) in the general population?

BPTF p.Pro2787= (c.8361A>T) is very rare (popmax 0.00223%, eas) (gnomAD).

BPTF p.Pro2787=

Q: What condition is associated with BPTF p.Pro2787= (c.8361A>T)?

BPTF p.Pro2787= (c.8361A>T) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

c.8361A>T · VCV4855295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.38	acceptor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.6	GERP -2.2, phastCons 1
Overall
CADD	7.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.19e-05% 1/1,614,214 alleles · very rare exomes 1/1,461,886 · genomes 0/152,328 · joint denominator

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.Pro2787=
Coding: c.8361A>T
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67964311 (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.Arg1322Ter Pathogenic/Likely pathogenic ★★ same condition
BPTF p.Arg2858Ter Pathogenic ★★ same condition
BPTF p.Arg2058Cys Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2858Gln Uncertain significance ★★ ⚠ same condition
BPTF p.Arg542Gln Uncertain significance ★★ same condition
BPTF p.Arg68Ser Uncertain significance ★★ ⚠ same condition
BPTF p.Asn452Ser 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-pro2787 (accessed [today's date]).

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