Is BPTF p.Pro2376Thr (c.7126C>A) pathogenic?

BPTF p.Pro2376Thr (c.7126C>A) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-12). AlphaMissense: likely benign (0.0685); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Pro2376Thr (c.7126C>A)?

BPTF p.Pro2376Thr (c.7126C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Pro2376Thr (c.7126C>A) in the general population?

BPTF p.Pro2376Thr (c.7126C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPTF p.Pro2376Thr (c.7126C>A)?

AlphaMissense predicts likely benign (score 0.0685) — an in-silico prediction, not a clinical call.

BPTF p.Pro2376Thr

c.7126C>A · rs145519434 · VCV1313428

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0685 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0685	likely benign
REVEL	0.183	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 4	GERP 2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	21.4	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 and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P2502T vs ClinVar P2376T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BPTF
Protein: p.Pro2376Thr
Coding: c.7126C>A
MANE Select: NM_182641
dbSNP: rs145519434
Type: single nucleotide variant
Location: chr17:67945834 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2376: the 'disordered' region

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.Pro2376Ala 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-pro2376thr (accessed [today's date]).

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