Is BPTF p.Pro2379Ser (c.7135C>T) pathogenic?

BPTF p.Pro2379Ser (c.7135C>T) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely benign (0.085); Very rare (popmax 0.00475%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Pro2379Ser (c.7135C>T)?

BPTF p.Pro2379Ser (c.7135C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Pro2379Ser (c.7135C>T) in the general population?

BPTF p.Pro2379Ser (c.7135C>T) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Pro2379Ser (c.7135C>T)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

BPTF p.Pro2379Ser

c.7135C>T · rs372837861 · VCV964075

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P2505S vs ClinVar P2379S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00475% European (non-Finnish) · 56/1,180,048 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00403% 65/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,811
European (non-Finnish)grpmax	0.00475%	21,072
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

Remaining individuals 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.Pro2379Ser
Coding: c.7135C>T
MANE Select: NM_182641
dbSNP: rs372837861
Type: single nucleotide variant
Location: chr17:67945843 (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.Pro2379Leu Uncertain significance ★ ⚠ same residue
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

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-pro2379ser (accessed [today's date]).

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