Is BMPER p.Pro222= (c.666C>T) pathogenic?

BMPER p.Pro222= (c.666C>T) is classified Likely benign in BMPER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-04). Very rare (popmax 0.000509%, nfe).

How common is BMPER p.Pro222= (c.666C>T) in the general population?

BMPER p.Pro222= (c.666C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

BMPER p.Pro222=

c.666C>T · VCV4895683

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.21, phastCons 1
Overall
CADD	11.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,646 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,684 alleles · very rare exomes 6/1,461,428 · genomes 0/152,256 · joint denominator

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.Pro222=
Coding: c.666C>T
MANE Select: NM_001365308
Type: single nucleotide variant
Location: chr7:34046395 (GRCh38)
Gene constraint: LOEUF 0.652 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.24
Residue 222: the vwfc 3 domain

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

Similar variants

BMPER p.Pro222Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro222 (accessed [today's date]).

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