Is BLTP3B p.Lys1087Glu (c.3259A>G) pathogenic?

BLTP3B p.Lys1087Glu (c.3259A>G) is classified Uncertain significance in BLTP3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely benign (0.1029); Very rare (popmax 0.00171%, amr).

How common is BLTP3B p.Lys1087Glu (c.3259A>G) in the general population?

BLTP3B p.Lys1087Glu (c.3259A>G) is very rare (popmax 0.00171%, amr) (gnomAD).

What do computational predictors say about BLTP3B p.Lys1087Glu (c.3259A>G)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

BLTP3B p.Lys1087Glu

c.3259A>G · VCV3481059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 51 kb · p 0.37 · regional, not allelic
Overall
CADD	21.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,648 alleles

Filtering AF 0.00036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000756% 11/1,454,266 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,648
Remaining individualsnot grpmax-eligible	0.00161%	62,166
European (non-Finnish)	0.000764%	130,858

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: BLTP3B
Protein: p.Lys1087Glu
Coding: c.3259A>G
MANE Select: NM_015054
Type: single nucleotide variant
Location: chr12:100057736 (GRCh38)
Structure: AlphaFold pLDDT 67.53
Residue 1087: the 'disordered' region

Full BLTP3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BLTP3B p.Leu491= Benign ★★ same type
BLTP3B p.Ala109Val Uncertain significance ★ ⚠ same type
BLTP3B p.Ala1162Thr Uncertain significance ★ ⚠ same type
BLTP3B p.Ala1272Ser Uncertain significance ★ ⚠ same type
BLTP3B p.Ala231Ser Uncertain significance ★ ⚠ same type
BLTP3B p.Ala231Thr Uncertain significance ★ ⚠ same type
BLTP3B p.Ala257Gly Uncertain significance ★ ⚠ same type
BLTP3B p.Ala66Thr Uncertain significance ★ ⚠ same type

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/bltp3b-p-lys1087glu (accessed [today's date]).

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