Is BPNT2 p.Arg229= (c.687C>T) pathogenic?

BPNT2 p.Arg229= (c.687C>T) is classified Uncertain significance in BPNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00223%, eas); Associated with chondrodysplasia with joint dislocations, gPAPP type.

What condition is associated with BPNT2 p.Arg229= (c.687C>T)?

BPNT2 p.Arg229= (c.687C>T) is associated with chondrodysplasia with joint dislocations, gPAPP type (ClinVar).

How common is BPNT2 p.Arg229= (c.687C>T) in the general population?

BPNT2 p.Arg229= (c.687C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

BPNT2 p.Arg229=

c.687C>T · rs886063019 · VCV363406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

chondrodysplasia with joint dislocations, gPAPP type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.03	GERP -1.1
Overall
CADD	6.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,862 alleles

Overall 6.84e-05% 1/1,461,666 alleles · very rare

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.Arg229=
Coding: c.687C>T
MANE Select: NM_017813
dbSNP: rs886063019
Type: single nucleotide variant
Location: chr8:56966312 (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

Disease context

chondrodysplasia with joint dislocations, gPAPP type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPNT2 p.Arg229Cys Uncertain significance ★ ⚠ same residue
BPNT2 p.Arg229His Uncertain significance ★ ⚠ same residue
BPNT2 p.Arg187Ter Pathogenic ★★ same condition
BPNT2 c.-155C>G Uncertain significance ★★ same condition
BPNT2 c.*4264G>A Uncertain significance ★★ same condition
BPNT2 c.*5193A>G Uncertain significance ★★ same condition
BPNT2 p.Ala218Ser Uncertain significance ★★ ⚠ same condition
BPNT2 p.Arg187Gln 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/bpnt2-p-arg229 (accessed [today's date]).

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