Is BMPER p.Arg131Cys (c.391C>T) pathogenic?

BMPER p.Arg131Cys (c.391C>T) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1237); Ultra-rare (popmax 0.0164%, mid); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Arg131Cys (c.391C>T)?

BMPER p.Arg131Cys (c.391C>T) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Arg131Cys (c.391C>T) in the general population?

BMPER p.Arg131Cys (c.391C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about BMPER p.Arg131Cys (c.391C>T)?

AlphaMissense predicts likely benign (score 0.1237) — an in-silico prediction, not a clinical call.

BMPER p.Arg131Cys

c.391C>T · rs374945016 · VCV910220

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1237 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
AlphaMissense	0.1237	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor loss · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 0.93
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	23.4	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00359% 58/1,613,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.01%	9,999
European (non-Finnish)	0.00373%	26,809
Remaining individualsnot grpmax-eligible	0.0032%	31,230
African / African-American	0.00267%	37,442
East Asian	0.00223%	44,882
Finnishnot grpmax-eligible	0.00156%	63,974
South Asian	0.0011%	91,076

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.Arg131Cys
Coding: c.391C>T
MANE Select: NM_001365308
dbSNP: rs374945016
Type: single nucleotide variant
Location: chr7:33966550 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 131: the vwfc 2 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.Ala486Val 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-arg131cys (accessed [today's date]).

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