Is BPTF p.Gln2095Arg (c.6284A>G) pathogenic?

BPTF p.Gln2095Arg (c.6284A>G) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-13). AlphaMissense: likely pathogenic (0.6); Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Gln2095Arg (c.6284A>G)?

BPTF p.Gln2095Arg (c.6284A>G) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Gln2095Arg (c.6284A>G) in the general population?

BPTF p.Gln2095Arg (c.6284A>G) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about BPTF p.Gln2095Arg (c.6284A>G)?

AlphaMissense predicts likely pathogenic (score 0.6) — an in-silico prediction, not a clinical call.

BPTF p.Gln2095Arg

c.6284A>G · rs199648024 · VCV598642

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6	likely pathogenic
REVEL	0.323	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	24.8	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 Q2221R vs ClinVar Q2095R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,886 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000558% 9/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,481
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	59,998

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.Gln2095Arg
Coding: c.6284A>G
MANE Select: NM_182641
dbSNP: rs199648024
Type: single nucleotide variant
Location: chr17:67940463 (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.Gln2095= Benign ★★ same residue
BPTF p.Gln2095Lys Uncertain significance ★ ⚠ same residue
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

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-gln2095arg (accessed [today's date]).

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