Is BMPER p.Met484Thr (c.1451T>C) pathogenic?

BMPER p.Met484Thr (c.1451T>C) is classified Likely benign in BMPER (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-10). AlphaMissense: likely benign (0.1072); Rare (popmax 0.233%, afr).

How common is BMPER p.Met484Thr (c.1451T>C) in the general population?

BMPER p.Met484Thr (c.1451T>C) is rare (popmax 0.233%, afr) (gnomAD).

What do computational predictors say about BMPER p.Met484Thr (c.1451T>C)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

BMPER p.Met484Thr

c.1451T>C · rs140406284 · VCV1539488

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.233%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -4.07	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 0.51	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 248 kb · p 0.0046 · regional, not allelic
Overall
CADD	16.33	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 0.233% African / African-American · 175/75,070 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.0114% 184/1,614,246 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.233%	429
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Admixed American	0.005%	20,009
European (non-Finnish)	0.000169%	590,023

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.Met484Thr
Coding: c.1451T>C
MANE Select: NM_001365308
dbSNP: rs140406284
Type: single nucleotide variant
Location: chr7:34085798 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 484: 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-met484thr (accessed [today's date]).

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