Is BPTF p.Ile2012Thr (c.6035T>C) pathogenic?

BPTF p.Ile2012Thr (c.6035T>C) is classified Conflicting classifications of pathogenicity in BPTF (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-05-01). AlphaMissense: likely pathogenic (0.9904); Ultra-rare (popmax 0.0417%, amr); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Ile2012Thr (c.6035T>C)?

BPTF p.Ile2012Thr (c.6035T>C) is associated with Inborn genetic diseases, Kaposi's sarcoma, Kaposi sarcoma, susceptibility to (ClinVar).

How common is BPTF p.Ile2012Thr (c.6035T>C) in the general population?

BPTF p.Ile2012Thr (c.6035T>C) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about BPTF p.Ile2012Thr (c.6035T>C)?

AlphaMissense predicts likely pathogenic (score 0.9904) — an in-silico prediction, not a clinical call.

BPTF p.Ile2012Thr

c.6035T>C · rs187498805 · VCV2077514

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9904 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9904	likely pathogenic · top 9% in BPTF
REVEL	0.474	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 2e-06 · regional, not allelic
Overall
CADD	24.7	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 I2138T vs ClinVar I2012T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0417% Admixed American · 25/60,006 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00353% 57/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.00212%	47,200
African / African-American	0.00133%	75,046

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.Ile2012Thr
Coding: c.6035T>C
MANE Select: NM_182641
dbSNP: rs187498805
Type: single nucleotide variant
Location: chr17:67929372 (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

Also linked: Kaposi's sarcoma Kaposi sarcoma, susceptibility to

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-ile2012thr (accessed [today's date]).

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