Is BPTF p.Pro239Ser (c.715C>T) pathogenic?

BPTF p.Pro239Ser (c.715C>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). AlphaMissense: ambiguous (0.5198); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Pro239Ser (c.715C>T)?

BPTF p.Pro239Ser (c.715C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Pro239Ser (c.715C>T) in the general population?

BPTF p.Pro239Ser (c.715C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BPTF p.Pro239Ser (c.715C>T)?

AlphaMissense predicts ambiguous (score 0.5198) — an in-silico prediction, not a clinical call.

BPTF p.Pro239Ser

c.715C>T · VCV3825218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5198	ambiguous
REVEL	0.642	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 512 bp · p 3.3e-14 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,984 alleles

Overall 0.000186% 3/1,614,014 alleles · very rare exomes 2/1,461,890 · genomes 1/152,124 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.47e-05%	1,180,038

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.Pro239Ser
Coding: c.715C>T
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67854041 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1078Gln Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg215His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2352His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2858Gln Uncertain significance ★★ ⚠ same condition
BPTF p.Arg68Ser 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-pro239ser (accessed [today's date]).

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