Is BPTF p.Ala116Glu (c.347C>A) pathogenic?

BPTF p.Ala116Glu (c.347C>A) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: ambiguous (0.4233); Very rare (popmax 0.00251%, amr).

How common is BPTF p.Ala116Glu (c.347C>A) in the general population?

BPTF p.Ala116Glu (c.347C>A) is very rare (popmax 0.00251%, amr) (gnomAD).

What do computational predictors say about BPTF p.Ala116Glu (c.347C>A)?

AlphaMissense predicts ambiguous (score 0.4233) — an in-silico prediction, not a clinical call.

BPTF p.Ala116Glu

c.347C>A · VCV3684577

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00251%, amr)

Computational evidence

Protein change
AlphaMissense	0.4233	ambiguous
REVEL	0.224	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -0.38, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 0.058 · regional, not allelic
Overall
CADD	21.9	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 0.00251% Admixed American · 1/39,818 alleles

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

Overall 0.000709% 8/1,128,472 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.013%	7,719
Remaining individualsnot grpmax-eligible	0.0041%	24,374
Admixed Americangrpmax	0.00251%	39,818
European (non-Finnish)	0.000211%	473,469

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala116Glu
Coding: c.347C>A
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67826071 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 116: the 'disordered' region

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

Similar variants

BPTF p.Ala116Val Likely benign ★ 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-ala116glu (accessed [today's date]).

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