Is BPTF p.Asp1225Val (c.3674A>T) pathogenic?

BPTF p.Asp1225Val (c.3674A>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1075); Ultra-rare (popmax 0.0307%, sas).

How common is BPTF p.Asp1225Val (c.3674A>T) in the general population?

BPTF p.Asp1225Val (c.3674A>T) is ultra-rare (popmax 0.0307%, sas) (gnomAD).

What do computational predictors say about BPTF p.Asp1225Val (c.3674A>T)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

BPTF p.Asp1225Val

c.3674A>T · VCV4768099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.274	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -2.4, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 7,708 bp · p 0.94 · regional, not allelic
Overall
CADD	16.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D1351V vs ClinVar D1225V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% South Asian · 28/91,076 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00192% 28/1,461,824 alleles · ultra-rare

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.Asp1225Val
Coding: c.3674A>T
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67911558 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1225: the 'disordered' region

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

Similar variants

BPTF p.Asp1225His Uncertain significance ★★ ⚠ same residue
BPTF p.Asp1225Thr Uncertain significance same residue
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

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-asp1225val (accessed [today's date]).

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