Is BPTF p.Pro2685= (c.8055T>A) pathogenic?

BPTF p.Pro2685= (c.8055T>A) is classified Likely benign in BPTF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-06-18). Very rare (popmax 0.00393%, eas); Associated with BPTF-related disorder.

What condition is associated with BPTF p.Pro2685= (c.8055T>A)?

BPTF p.Pro2685= (c.8055T>A) is associated with BPTF-related disorder (ClinVar).

How common is BPTF p.Pro2685= (c.8055T>A) in the general population?

BPTF p.Pro2685= (c.8055T>A) is very rare (popmax 0.00393%, eas) (gnomAD).

BPTF p.Pro2685=

c.8055T>A · rs1555682939 · VCV3051404

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00393%, eas)

Conditions

BPTF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -4.1
Overall
CADD	0.986	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00393% East Asian · 1/25,418 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000555% 6/1,081,488 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00438%	22,844
East Asiangrpmax	0.00393%	25,418
Admixed American	0.00266%	37,604
Remaining individualsnot grpmax-eligible	0.00223%	44,858
European (non-Finnish)	0.000229%	435,791

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.Pro2685=
Coding: c.8055T>A
MANE Select: NM_182641
dbSNP: rs1555682939
Type: single nucleotide variant
Location: chr17:67959669 (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

BPTF-related disorder

Similar variants

BPTF p.Pro2685Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BPTF p.Leu935Phe Uncertain significance ★★ ⚠ same condition
BPTF p.Ala83Gly Uncertain significance ★ ⚠ same condition
BPTF p.Ile2057Asn Uncertain significance ★ same condition
BPTF p.Ile218Thr Uncertain significance ★ same condition
BPTF p.Lys1445Asn Uncertain significance ★ ⚠ same condition
BPTF p.Met324Leu Uncertain significance ★ same condition
BPTF p.Ser1154Arg 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-pro2685 (accessed [today's date]).

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