Is BPNT2 p.Lys149Glu (c.445A>G) pathogenic?

BPNT2 p.Lys149Glu (c.445A>G) is classified Uncertain significance in BPNT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-10). AlphaMissense: likely benign (0.0795); Rare (popmax 0.116%, afr).

How common is BPNT2 p.Lys149Glu (c.445A>G) in the general population?

BPNT2 p.Lys149Glu (c.445A>G) is rare (popmax 0.116%, afr) (gnomAD).

What do computational predictors say about BPNT2 p.Lys149Glu (c.445A>G)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

BPNT2 p.Lys149Glu

c.445A>G · rs148440829 · VCV2068711

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -8.89	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 4.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.51 · regional, not allelic
Overall
CADD	18.28	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 0.116% African / African-American · 87/75,032 alleles

Filtering AF 0.0963% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.089%

Overall 0.00626% 101/1,613,710 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.116%	862
Admixed American	0.015%	6,670
Remaining individualsnot grpmax-eligible	0.0048%	20,826
European (non-Finnish)	0.00017%	589,824

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: BPNT2
Protein: p.Lys149Glu
Coding: c.445A>G
MANE Select: NM_017813
dbSNP: rs148440829
Type: single nucleotide variant
Location: chr8:56980140 (GRCh38)
Gene constraint: LOEUF 0.619 · pLI 0.79 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.55

Full BPNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BPNT2 p.Arg187Ter Pathogenic ★★ same type
BPNT2 c.-155C>G Uncertain significance ★★ same type
BPNT2 c.*4264G>A Uncertain significance ★★ same type
BPNT2 c.*5193A>G Uncertain significance ★★ same type
BPNT2 p.Ala218Ser Uncertain significance ★★ ⚠ same type
BPNT2 p.Arg187Gln Uncertain significance ★★ ⚠ same type
BPNT2 p.Arg243Cys Uncertain significance ★★ ⚠ same type
BPNT2 p.Arg243His 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/bpnt2-p-lys149glu (accessed [today's date]).

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