Is BPTF p.Ile855Thr (c.2564T>C) pathogenic?

BPTF p.Ile855Thr (c.2564T>C) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: ambiguous (0.5156); Very rare (popmax 0.00146%, nfe).

How common is BPTF p.Ile855Thr (c.2564T>C) in the general population?

BPTF p.Ile855Thr (c.2564T>C) is very rare (popmax 0.00146%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Ile855Thr (c.2564T>C)?

AlphaMissense predicts ambiguous (score 0.5156) — an in-silico prediction, not a clinical call.

BPTF p.Ile855Thr

c.2564T>C · rs1249984546 · VCV2870845

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5156 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00146%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5156	ambiguous
REVEL	0.328	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 11 kb · p 1.9e-17 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I981T vs ClinVar I855T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00146% European (non-Finnish) · 17/1,167,360 alleles

Filtering AF 0.000887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000725%

Overall 0.00114% 18/1,576,728 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00146%	68,668
South Asian	0.0012%	83,362

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.Ile855Thr
Coding: c.2564T>C
MANE Select: NM_182641
dbSNP: rs1249984546
Type: single nucleotide variant
Location: chr17:67903809 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 855: the 'interaction with maz' region

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

Similar variants

BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ same type
BPTF p.Arg1738Ter Pathogenic/Likely pathogenic ★★ same type
BPTF p.Arg2858Ter Pathogenic ★★ same type
BPTF p.Arg841Ter Pathogenic ★★ same type
BPTF c.1864+562A>T Uncertain significance ★★ same type
BPTF c.1865-5651C>G Uncertain significance ★★ ⚠ same type
BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same type
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same type

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-ile855thr (accessed [today's date]).

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