Is BPTF p.Ile2011Val (c.6031A>G) pathogenic?

BPTF p.Ile2011Val (c.6031A>G) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-28). AlphaMissense: ambiguous (0.4186); Ultra-rare (popmax 0.0254%, afr).

How common is BPTF p.Ile2011Val (c.6031A>G) in the general population?

BPTF p.Ile2011Val (c.6031A>G) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about BPTF p.Ile2011Val (c.6031A>G)?

AlphaMissense predicts ambiguous (score 0.4186) — an in-silico prediction, not a clinical call.

BPTF p.Ile2011Val

c.6031A>G · VCV3698661

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4186 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Computational evidence

Protein change
AlphaMissense	0.4186	ambiguous
REVEL	0.124	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 2e-06 · regional, not allelic
Overall
CADD	22.3	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 I2137V vs ClinVar I2011V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0254% African / African-American · 19/74,930 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00136% 22/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,944
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000169%	590,012

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.Ile2011Val
Coding: c.6031A>G
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67929368 (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

Similar variants

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BPTF p.Arg841Ter Pathogenic ★★ same type
BPTF c.1864+562A>T Uncertain significance ★★ same type
BPTF c.1865-5651C>G Uncertain significance ★★ ⚠ same type
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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-ile2011val (accessed [today's date]).

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