Is BPTF p.Ala2589Val (c.7766C>T) pathogenic?

BPTF p.Ala2589Val (c.7766C>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-30). AlphaMissense: ambiguous (0.3447); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Ala2589Val (c.7766C>T)?

BPTF p.Ala2589Val (c.7766C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Ala2589Val (c.7766C>T) in the general population?

BPTF p.Ala2589Val (c.7766C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPTF p.Ala2589Val (c.7766C>T)?

AlphaMissense predicts ambiguous (score 0.3447) — an in-silico prediction, not a clinical call.

BPTF p.Ala2589Val

c.7766C>T · rs2065952071 · VCV3134909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3447	ambiguous
REVEL	0.234	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 418 bp · p 8.7e-06 · regional, not allelic
Overall
CADD	29.2	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 A2715V vs ClinVar A2589V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BPTF
Protein: p.Ala2589Val
Coding: c.7766C>T
MANE Select: NM_182641
dbSNP: rs2065952071
Type: single nucleotide variant
Location: chr17:67948146 (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-ala2589val (accessed [today's date]).

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