Is BPTF p.Ala672Thr (c.2014G>A) pathogenic?

BPTF p.Ala672Thr (c.2014G>A) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). AlphaMissense: ambiguous (0.4185); Very rare (popmax 0.0017%, amr); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Ala672Thr (c.2014G>A)?

BPTF p.Ala672Thr (c.2014G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Ala672Thr (c.2014G>A) in the general population?

BPTF p.Ala672Thr (c.2014G>A) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about BPTF p.Ala672Thr (c.2014G>A)?

AlphaMissense predicts ambiguous (score 0.4185) — an in-silico prediction, not a clinical call.

BPTF p.Ala672Thr

c.2014G>A · VCV3825220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4185	ambiguous
REVEL	0.277	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 6, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 1,547 bp · p 0.022 · regional, not allelic
Overall
CADD	29.1	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 A798T vs ClinVar A672T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,796 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000436% 7/1,606,222 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,796
Remaining individualsnot grpmax-eligible	0.00161%	62,100
African / African-American	0.00134%	74,390
South Asian	0.00112%	89,684
European (non-Finnish)	0.000255%	392,272

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.Ala672Thr
Coding: c.2014G>A
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67891993 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 672: the 'disordered' region; the 'interaction with keap1' region

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-ala672thr (accessed [today's date]).

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