Is BMPER p.Val575Ala (c.1724T>C) pathogenic?

BMPER p.Val575Ala (c.1724T>C) is classified Uncertain significance in BMPER (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-20). AlphaMissense: likely benign (0.2336); Ultra-rare (popmax 0.033%, mid); Associated with diaphanospondylodysostosis.

What condition is associated with BMPER p.Val575Ala (c.1724T>C)?

BMPER p.Val575Ala (c.1724T>C) is associated with diaphanospondylodysostosis (ClinVar).

How common is BMPER p.Val575Ala (c.1724T>C) in the general population?

BMPER p.Val575Ala (c.1724T>C) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about BMPER p.Val575Ala (c.1724T>C)?

AlphaMissense predicts likely benign (score 0.2336) — an in-silico prediction, not a clinical call.

BMPER p.Val575Ala

c.1724T>C · rs760584340 · VCV360114

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2336 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

diaphanospondylodysostosis

Computational evidence

Protein change
AlphaMissense	0.2336	likely benign
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -12.62	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	23.6	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 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00378% 61/1,613,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
Admixed American	0.00667%	15,001
European (non-Finnish)	0.00458%	21,852
Finnishnot grpmax-eligible	0.00156%	63,918

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.Val575Ala
Coding: c.1724T>C
MANE Select: NM_001365308
dbSNP: rs760584340
Type: single nucleotide variant
Location: chr7:34086071 (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.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
BMPER p.Arg582Trp 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-val575ala (accessed [today's date]).

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