Is BPTF p.Pro887Ser (c.2659C>T) pathogenic?

BPTF p.Pro887Ser (c.2659C>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.974); Very rare (popmax 8.53e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Pro887Ser (c.2659C>T)?

BPTF p.Pro887Ser (c.2659C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Pro887Ser (c.2659C>T) in the general population?

BPTF p.Pro887Ser (c.2659C>T) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Pro887Ser (c.2659C>T)?

AlphaMissense predicts likely pathogenic (score 0.974) — an in-silico prediction, not a clinical call.

BPTF p.Pro887Ser

c.2659C>T · VCV4215006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.974	likely pathogenic
REVEL	0.497	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.33	donor gain · deltas
Pangolin	Δ0.24	gain · loss 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 11 kb · p 1.9e-17 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1013S vs ClinVar P887S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,172,046 alleles

Overall 6.31e-05% 1/1,584,220 alleles · very rare exomes 1/1,431,932 · genomes 0/152,288 · 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.Pro887Ser
Coding: c.2659C>T
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67903904 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1078Gln Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg215His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2352His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2858Gln Uncertain significance ★★ ⚠ same condition
BPTF p.Arg68Ser 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-pro887ser (accessed [today's date]).

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