Is BPTF p.Glu985Gln (c.2953G>C) pathogenic?

BPTF p.Glu985Gln (c.2953G>C) is classified Benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). AlphaMissense: likely benign (0.1116); Very rare (popmax 0.000342%, nfe).

How common is BPTF p.Glu985Gln (c.2953G>C) in the general population?

BPTF p.Glu985Gln (c.2953G>C) is very rare (popmax 0.000342%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Glu985Gln (c.2953G>C)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

BPTF p.Glu985Gln

c.2953G>C · rs1382232978 · VCV2093643

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000342%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.114	moderately 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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 7,708 bp · p 0.94 · regional, not allelic
Overall
CADD	22.4	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 E1111Q vs ClinVar E985Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000342% European (non-Finnish) · 4/1,170,868 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000252% 4/1,588,266 alleles · very 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.Glu985Gln
Coding: c.2953G>C
MANE Select: NM_182641
dbSNP: rs1382232978
Type: single nucleotide variant
Location: chr17:67909722 (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-glu985gln (accessed [today's date]).

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