Is BPTF p.Pro2672Ala (c.8014C>G) pathogenic?

BPTF p.Pro2672Ala (c.8014C>G) is classified Benign/Likely benign in BPTF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.046); Ultra-rare (popmax 0.0815%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Pro2672Ala (c.8014C>G)?

BPTF p.Pro2672Ala (c.8014C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Pro2672Ala (c.8014C>G) in the general population?

BPTF p.Pro2672Ala (c.8014C>G) is ultra-rare (popmax 0.0815%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Pro2672Ala (c.8014C>G)?

AlphaMissense predicts likely benign (score 0.046) — an in-silico prediction, not a clinical call.

BPTF p.Pro2672Ala

c.8014C>G · rs142300680 · VCV2040686

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.046 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0815%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.046	likely benign
REVEL	0.042	moderately 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 0.43	GERP -4.1, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.83 · regional, not allelic
Overall
CADD	7.058	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P2798A vs ClinVar P2672A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0815% European (non-Finnish) · 957/1,174,642 alleles

Filtering AF 0.0772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0754%

Overall 0.0656% 1,049/1,598,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0815%	1,227
Remaining individualsnot grpmax-eligible	0.0534%	1,872
Admixed American	0.0533%	1,875
Middle Eastern	0.0503%	1,989
Finnishnot grpmax-eligible	0.0299%	3,340
African / African-American	0.00811%	12,329
East Asian	0.00226%	44,332

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.Pro2672Ala
Coding: c.8014C>G
MANE Select: NM_182641
dbSNP: rs142300680
Type: single nucleotide variant
Location: chr17:67959628 (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.Pro2672Arg 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-pro2672ala (accessed [today's date]).

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