Is BMPER p.Cys599= (c.1797C>T) pathogenic?

BMPER p.Cys599= (c.1797C>T) is classified Benign/Likely benign in BMPER (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.02%, mid); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Cys599= (c.1797C>T)?

BMPER p.Cys599= (c.1797C>T) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Cys599= (c.1797C>T) in the general population?

BMPER p.Cys599= (c.1797C>T) is low-frequency (popmax 1.02%, mid) (gnomAD).

BMPER p.Cys599=

c.1797C>T · rs74674953 · VCV360115

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, mid)

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -5.5
Overall
CADD	4.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.02% Middle Eastern · 62/6,062 alleles

Filtering AF 0.819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.745%

Overall 0.572% 9,236/1,613,974 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.99%	50
Middle Easterngrpmax	1.02%	98
Remaining individualsnot grpmax-eligible	0.698%	143
European (non-Finnish)	0.625%	160
South Asian	0.442%	226
Admixed American	0.348%	287
African / African-American	0.117%	852
Finnishnot grpmax-eligible	0.108%	928

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: BMPER
Protein: p.Cys599=
Coding: c.1797C>T
MANE Select: NM_001365308
dbSNP: rs74674953
Type: single nucleotide variant
Location: chr7:34143281 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24

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.Cys599Ser Uncertain significance ★ ⚠ same residue
BMPER p.Cys599Trp Uncertain significance ★ ⚠ 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

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-cys599 (accessed [today's date]).

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