Is BPTF p.Asp1752Ala (c.5255A>C) pathogenic?

BPTF p.Asp1752Ala (c.5255A>C) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-21). AlphaMissense: likely pathogenic (0.9711); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

What condition is associated with BPTF p.Asp1752Ala (c.5255A>C)?

BPTF p.Asp1752Ala (c.5255A>C) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.Asp1752Ala (c.5255A>C) in the general population?

BPTF p.Asp1752Ala (c.5255A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPTF p.Asp1752Ala (c.5255A>C)?

AlphaMissense predicts likely pathogenic (score 0.9711) — an in-silico prediction, not a clinical call.

BPTF p.Asp1752Ala

c.5255A>C · VCV3901944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9711 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Computational evidence

Protein change
AlphaMissense	0.9711	likely pathogenic
REVEL	0.515	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 5,608 bp · p 0.83 · regional, not allelic
Overall
CADD	25.8	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 D1878A vs ClinVar D1752A) — 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.Asp1752Ala
Coding: c.5255A>C
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67913139 (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-asp1752ala (accessed [today's date]).

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