Is BMPER p.Asp457Glu (c.1371C>G) pathogenic?

BMPER p.Asp457Glu (c.1371C>G) is classified Uncertain significance in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.194); Very rare (popmax 0.00439%, sas).

How common is BMPER p.Asp457Glu (c.1371C>G) in the general population?

BMPER p.Asp457Glu (c.1371C>G) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about BMPER p.Asp457Glu (c.1371C>G)?

AlphaMissense predicts likely benign (score 0.194) — an in-silico prediction, not a clinical call.

BMPER p.Asp457Glu

c.1371C>G · rs758083898 · VCV1419031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.194 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.194	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -6.10	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 2.6	GERP -0.062, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	19.25	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 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000684% 10/1,461,636 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,502
South Asiangrpmax	0.00439%	22,772
European (non-Finnish)	8.47e-05%	1,180,018

Remaining individuals 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.Asp457Glu
Coding: c.1371C>G
MANE Select: NM_001365308
dbSNP: rs758083898
Type: single nucleotide variant
Location: chr7:34079149 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 457: a disulfide bond; the vwfd domain

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

Similar variants

BMPER p.Arg241Ter Likely pathogenic ★★ same type
BMPER p.Gln309Ter Pathogenic ★★ same type
BMPER p.Ala39Ser Uncertain significance ★★ ⚠ same type
BMPER p.Ala486Val Uncertain significance ★★ ⚠ same type
BMPER p.Arg131Cys Uncertain significance ★★ ⚠ same type
BMPER p.Arg16Ser Uncertain significance ★★ ⚠ same type
BMPER p.Arg332His Uncertain significance ★★ ⚠ same type
BMPER p.Arg410His Uncertain significance ★★ ⚠ same type

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-asp457glu (accessed [today's date]).

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