Is BMPER p.Asp243Val (c.728A>T) pathogenic?

BMPER p.Asp243Val (c.728A>T) is classified Uncertain significance in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.161); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BMPER p.Asp243Val (c.728A>T)?

BMPER p.Asp243Val (c.728A>T) is associated with Inborn genetic diseases (ClinVar).

How common is BMPER p.Asp243Val (c.728A>T) in the general population?

BMPER p.Asp243Val (c.728A>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about BMPER p.Asp243Val (c.728A>T)?

AlphaMissense predicts likely benign (score 0.161) — an in-silico prediction, not a clinical call.

BMPER p.Asp243Val

c.728A>T · VCV4596876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.161	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	22.7	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 0.00017% European (non-Finnish) · 2/1,179,904 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,734 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.Asp243Val
Coding: c.728A>T
MANE Select: NM_001365308
Type: single nucleotide variant
Location: chr7:34051912 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 243: the vwfc 4 domain

Full BMPER gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg16Ser Uncertain significance ★★ ⚠ same condition
BMPER p.Arg332His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg410His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg505His Uncertain significance ★★ ⚠ same condition
BMPER p.Arg558Gln Uncertain significance ★★ ⚠ same condition
BMPER p.Arg582Gln Uncertain significance ★★ ⚠ same condition
BMPER p.Asn65Lys 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-asp243val (accessed [today's date]).

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