Is BMPER p.Ala486Val (c.1457C>T) pathogenic?

BMPER p.Ala486Val (c.1457C>T) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-14). AlphaMissense: likely benign (0.187); Ultra-rare (popmax 0.099%, mid); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Ala486Val (c.1457C>T)?

BMPER p.Ala486Val (c.1457C>T) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Ala486Val (c.1457C>T) in the general population?

BMPER p.Ala486Val (c.1457C>T) is ultra-rare (popmax 0.099%, mid) (gnomAD).

What do computational predictors say about BMPER p.Ala486Val (c.1457C>T)?

AlphaMissense predicts likely benign (score 0.187) — an in-silico prediction, not a clinical call.

BMPER p.Ala486Val

c.1457C>T · rs368522901 · VCV911319

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.187 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
AlphaMissense	0.187	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00917% 148/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
South Asian	0.056%	1,786
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.00644%	15,526
Admixed American	0.005%	20,007
Finnishnot grpmax-eligible	0.00312%	32,011
African / African-American	0.00267%	37,512
East Asian	0.00223%	44,876

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.Ala486Val
Coding: c.1457C>T
MANE Select: NM_001365308
dbSNP: rs368522901
Type: single nucleotide variant
Location: chr7:34085804 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 486: 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.Arg241Ter Likely pathogenic ★★ same condition
BMPER p.Gln309Ter Pathogenic ★★ same condition
BMPER p.Ala39Ser 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
BMPER p.Arg582Trp Uncertain significance ★★ ⚠ same condition
BMPER p.Arg685Gln 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-ala486val (accessed [today's date]).

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