Is BPTF p.Asp2509Val (c.7526A>T) pathogenic?

BPTF p.Asp2509Val (c.7526A>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-27). AlphaMissense: ambiguous (0.3548); Absent from gnomAD v4.1; Associated with syndromic intellectual disability.

What condition is associated with BPTF p.Asp2509Val (c.7526A>T)?

BPTF p.Asp2509Val (c.7526A>T) is associated with syndromic intellectual disability (ClinVar).

How common is BPTF p.Asp2509Val (c.7526A>T) in the general population?

BPTF p.Asp2509Val (c.7526A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPTF p.Asp2509Val (c.7526A>T)?

AlphaMissense predicts ambiguous (score 0.3548) — an in-silico prediction, not a clinical call.

BPTF p.Asp2509Val

c.7526A>T · VCV3778911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3548 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

syndromic intellectual disability

Computational evidence

Protein change
AlphaMissense	0.3548	ambiguous
REVEL	0.122	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	22.7	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 D2635V vs ClinVar D2509V) — 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.Asp2509Val
Coding: c.7526A>T
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67946234 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2509: the 'disordered' region

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

Disease context

syndromic intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Pro1802Ala Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1199Gly Uncertain significance ★ ⚠ same condition
BPTF p.Ile2473Val Uncertain significance ★ ⚠ same condition
BPTF p.Lys398Arg Conflicting classifications of pathogenicity ★ same condition
BPTF p.Lys546Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
BPTF p.Pro615Ala Uncertain significance ★ ⚠ same condition
BPTF p.Pro2677_Pro2678insAlaAlaProProAlaPro Uncertain significance ★ same condition
BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ 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-asp2509val (accessed [today's date]).

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