Is BPNT2 p.Val347= (c.1041C>T) pathogenic?

BPNT2 p.Val347= (c.1041C>T) is classified Conflicting classifications of pathogenicity in BPNT2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-02). Ultra-rare (popmax 0.0493%, mid); Associated with chondrodysplasia with joint dislocations, gPAPP type.

What condition is associated with BPNT2 p.Val347= (c.1041C>T)?

BPNT2 p.Val347= (c.1041C>T) is associated with chondrodysplasia with joint dislocations, gPAPP type (ClinVar).

How common is BPNT2 p.Val347= (c.1041C>T) in the general population?

BPNT2 p.Val347= (c.1041C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

BPNT2 p.Val347=

c.1041C>T · rs372925433 · VCV909435

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.5	GERP 0.78, phastCons 1
Overall
CADD	7.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00781% 126/1,613,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.196%	510
Middle Easterngrpmax	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Admixed American	0.01%	10,002
Finnishnot grpmax-eligible	0.00781%	12,804
European (non-Finnish)	0.00314%	31,893
East Asian	0.00223%	44,878

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val347=
Coding: c.1041C>T
MANE Select: NM_017813
dbSNP: rs372925433
Type: single nucleotide variant
Location: chr8:56963832 (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-val347 (accessed [today's date]).

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