Is BMPER p.Gly136Ser (c.406G>A) pathogenic?

BMPER p.Gly136Ser (c.406G>A) is classified Uncertain significance in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: ambiguous (0.544); Very rare (popmax 0.000424%, nfe); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Gly136Ser (c.406G>A)?

BMPER p.Gly136Ser (c.406G>A) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Gly136Ser (c.406G>A) in the general population?

BMPER p.Gly136Ser (c.406G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about BMPER p.Gly136Ser (c.406G>A)?

AlphaMissense predicts ambiguous (score 0.544) — an in-silico prediction, not a clinical call.

BMPER p.Gly136Ser

c.406G>A · rs886062296 · VCV360100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
AlphaMissense	0.544	ambiguous
REVEL	0.569	indeterminate
SaProt	LLR -8.44	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	26.3	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 0.000424% European (non-Finnish) · 5/1,179,692 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,600 alleles · very rare

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.Gly136Ser
Coding: c.406G>A
MANE Select: NM_001365308
dbSNP: rs886062296
Type: single nucleotide variant
Location: chr7:33970332 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 136: 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.Gly136= Benign/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-gly136ser (accessed [today's date]).

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