Is BPTF p.Arg118Gln (c.353G>A) pathogenic?

BPTF p.Arg118Gln (c.353G>A) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely benign (0.258); Very rare (popmax 0.00234%, amr).

How common is BPTF p.Arg118Gln (c.353G>A) in the general population?

BPTF p.Arg118Gln (c.353G>A) is very rare (popmax 0.00234%, amr) (gnomAD).

What do computational predictors say about BPTF p.Arg118Gln (c.353G>A)?

AlphaMissense predicts likely benign (score 0.258) — an in-silico prediction, not a clinical call.

BPTF p.Arg118Gln

c.353G>A · rs1298970981 · VCV2580409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.258 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00234%, amr)

Computational evidence

Protein change
AlphaMissense	0.258	likely benign
REVEL	0.32	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.45, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 0.058 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00234% Admixed American · 1/42,686 alleles

Filtering AF 3.5e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3e-05%

Overall 0.000439% 5/1,139,998 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00234%	42,686
Remaining individualsnot grpmax-eligible	0.00202%	49,442
South Asian	0.00144%	69,520
European (non-Finnish)	0.000211%	473,525

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.Arg118Gln
Coding: c.353G>A
MANE Select: NM_182641
dbSNP: rs1298970981
Type: single nucleotide variant
Location: chr17:67826077 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 118: the 'disordered' region

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

Similar variants

BPTF p.Arg118Trp 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
BPTF p.Ala1197Val 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-arg118gln (accessed [today's date]).

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