Is BPTF p.Arg1833Gln (c.5498G>A) pathogenic?

BPTF p.Arg1833Gln (c.5498G>A) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely pathogenic (0.8206); Very rare (popmax 0.00223%, eas).

How common is BPTF p.Arg1833Gln (c.5498G>A) in the general population?

BPTF p.Arg1833Gln (c.5498G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BPTF p.Arg1833Gln (c.5498G>A)?

AlphaMissense predicts likely pathogenic (score 0.8206) — an in-silico prediction, not a clinical call.

BPTF p.Arg1833Gln

c.5498G>A · rs556375365 · VCV2648142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.8206	likely pathogenic
REVEL	0.458	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 2e-06 · regional, not allelic
Overall
CADD	33.0	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 R1959Q vs ClinVar R1833Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,832 alleles

Overall 0.000186% 3/1,611,778 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,832
Admixed American	0.00167%	59,958
European (non-Finnish)	8.49e-05%	1,178,080

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.Arg1833Gln
Coding: c.5498G>A
MANE Select: NM_182641
dbSNP: rs556375365
Type: single nucleotide variant
Location: chr17:67920084 (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

Similar variants

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
BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same type
BPTF p.Ala1252Val 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-arg1833gln (accessed [today's date]).

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