Is BPNT2 p.Leu336Pro (c.1007T>C) pathogenic?

BPNT2 p.Leu336Pro (c.1007T>C) is classified Likely pathogenic in BPNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.97); Absent from gnomAD v4.1; Associated with chondrodysplasia with joint dislocations, gPAPP type.

What condition is associated with BPNT2 p.Leu336Pro (c.1007T>C)?

BPNT2 p.Leu336Pro (c.1007T>C) is associated with chondrodysplasia with joint dislocations, gPAPP type (ClinVar).

How common is BPNT2 p.Leu336Pro (c.1007T>C) in the general population?

BPNT2 p.Leu336Pro (c.1007T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPNT2 p.Leu336Pro (c.1007T>C)?

AlphaMissense predicts likely pathogenic (score 0.97) — an in-silico prediction, not a clinical call.

BPNT2 p.Leu336Pro

c.1007T>C · rs1805889752 · VCV3068283

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.97 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chondrodysplasia with joint dislocations, gPAPP type

Computational evidence

Protein change
AlphaMissense	0.97	likely pathogenic ✓ concordant with ClinVar
REVEL	0.652	pathogenic-leaning
SaProt	LLR -17.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.51 · regional, not allelic
Overall
CADD	28.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BPNT2
Protein: p.Leu336Pro
Coding: c.1007T>C
MANE Select: NM_017813
dbSNP: rs1805889752
Type: single nucleotide variant
Location: chr8:56963866 (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.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
BPNT2 p.Gly330Ser Uncertain significance ★★ ⚠ same condition
BPNT2 p.Lys235Arg 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-leu336pro (accessed [today's date]).

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