Is BMPER p.Thr139= (c.417A>T) pathogenic?

BMPER p.Thr139= (c.417A>T) is classified Benign/Likely benign in BMPER (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-01). Rare (popmax 0.836%, nfe); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Thr139= (c.417A>T)?

BMPER p.Thr139= (c.417A>T) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Thr139= (c.417A>T) in the general population?

BMPER p.Thr139= (c.417A>T) is rare (popmax 0.836%, nfe) (gnomAD).

BMPER p.Thr139=

c.417A>T · rs147600292 · VCV770373

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.836%, nfe)

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.042	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4.2
Overall
CADD	0.391	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.836% European (non-Finnish) · 9,868/1,179,940 alleles

Filtering AF 0.822% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.817%

Overall 0.663% 10,707/1,614,082 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.836%	120
Remaining individualsnot grpmax-eligible	0.698%	143
Admixed American	0.307%	326
Amishnot grpmax-eligible	0.219%	456
African / African-American	0.128%	782
Finnishnot grpmax-eligible	0.0734%	1,362
Middle Eastern	0.066%	1,516
South Asian	0.0593%	1,687
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
East Asian	0.00446%	22,431

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.Thr139=
Coding: c.417A>T
MANE Select: NM_001365308
dbSNP: rs147600292
Type: single nucleotide variant
Location: chr7:33970343 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 139: 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.Thr139Arg Likely pathogenic ★ ⚠ same residue
BMPER p.Thr139Ala 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-thr139 (accessed [today's date]).

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