Is BPNT2 p.Ala2Asp (c.5C>A) pathogenic?

BPNT2 p.Ala2Asp (c.5C>A) is classified Uncertain significance in BPNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). AlphaMissense: likely pathogenic (0.8654); Very rare (popmax 0.000183%, nfe).

How common is BPNT2 p.Ala2Asp (c.5C>A) in the general population?

BPNT2 p.Ala2Asp (c.5C>A) is very rare (popmax 0.000183%, nfe) (gnomAD).

What do computational predictors say about BPNT2 p.Ala2Asp (c.5C>A)?

AlphaMissense predicts likely pathogenic (score 0.8654) — an in-silico prediction, not a clinical call.

BPNT2 p.Ala2Asp

c.5C>A · rs2129207484 · VCV1053543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000183%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8654	likely pathogenic
REVEL	0.297	indeterminate
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 0.49, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.51 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000183% European (non-Finnish) · 2/1,091,296 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000139% 2/1,437,390 alleles · very rare exomes 2/1,286,026 · genomes 0/151,364 · joint denominator

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.Ala2Asp
Coding: c.5C>A
MANE Select: NM_017813
dbSNP: rs2129207484
Type: single nucleotide variant
Location: chr8:56993581 (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.Ala2= Likely benign ★ same residue
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

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-ala2asp (accessed [today's date]).

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