Is BMPER p.Pro487Leu (c.1460C>T) pathogenic?

BMPER p.Pro487Leu (c.1460C>T) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-19). AlphaMissense: likely benign (0.3311); Rare (popmax 0.14%, nfe); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Pro487Leu (c.1460C>T)?

BMPER p.Pro487Leu (c.1460C>T) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Pro487Leu (c.1460C>T) in the general population?

BMPER p.Pro487Leu (c.1460C>T) is rare (popmax 0.14%, nfe) (gnomAD).

What do computational predictors say about BMPER p.Pro487Leu (c.1460C>T)?

AlphaMissense predicts likely benign (score 0.3311) — an in-silico prediction, not a clinical call.

BMPER p.Pro487Leu

c.1460C>T · rs115364786 · VCV360111

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3311 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.14%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
AlphaMissense	0.3311	likely benign
REVEL	0.496	indeterminate
SaProt	LLR -11.60	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	28.1	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 0.14% European (non-Finnish) · 1,648/1,180,034 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.109% 1,763/1,614,134 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.14%	716
Remaining individualsnot grpmax-eligible	0.109%	919
African / African-American	0.0387%	2,587
Admixed American	0.0167%	6,001
East Asian	0.00669%	14,957
Finnishnot grpmax-eligible	0.00625%	16,009
South Asian	0.0011%	91,078

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: BMPER
Protein: p.Pro487Leu
Coding: c.1460C>T
MANE Select: NM_001365308
dbSNP: rs115364786
Type: single nucleotide variant
Location: chr7:34085807 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 487: a disulfide bond; the vwfd domain

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

Disease context

diaphanospondylodysostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPER p.Pro487= Likely benign ★ same residue
BMPER p.Arg241Ter Likely pathogenic ★★ same condition
BMPER p.Gln309Ter Pathogenic ★★ same condition
BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Ala486Val Uncertain significance ★★ ⚠ same condition
BMPER p.Arg131Cys Uncertain significance ★★ ⚠ same condition
BMPER p.Arg505His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg582Gln 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/bmper-p-pro487leu (accessed [today's date]).

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